Herbicide compositions

ABSTRACT

A herbicidal composition which comprises i) an isoxazoline derivative represented by the following general formula (I) or its salt and ii) at least one compound selected from the Group A: 
 
Formula (I)  
                 
 
wherein R 1 , R 2 , R 3 , R 4 , R 5  and R 6  are defined in the specification.

TECHNICAL FIELD

The present invention relates to a herbicidal composition.

BACKGROUND ART

As a result of research and development for a long time, various kindsof various agrochemicals have been developed and practically used, andthese herbicides have contributed to improvement in productivity ofagricultural crops or contributed to elimination or reduction of laborof removing weeds. However even today, it is demanded to develop a newagrochemical having a more satisfactory herbicidal property.

It is demanded to provide a herbicidal agent used for useful crops,which achieves a satisfactory herbicidal effect at a small dose and hasan excellent selectivity between aimed crops and weeds by being appliedto soil or plant foliage.

DISCLOSURE OF THE INVENTION

An isoxazoline compound of the formula (I) which is one of activeingredients in the herbicidal composition of the present invention issafe to rice, wheat, barley, corn, grain sorghum, soybeans, cotton,sugar beet, turf, fruit trees and the like, and has an excellentherbicidal effect by itself.

The present inventors have discovered that by combining an isoxazolinederivative of the formula (I) with at least one herbicide of Group A ata predetermined ratio, not a simple total herbicidal effect but asynergistic herbicidal effect can be achieved. Thus, by combining atleast two agrochemical agents, a herbicidal spectrum is broadened ascompared with a herbicidal application range by each agent, and aherbicidal effect is achieved at an earlier stage and is retained for alonger time, and a satisfactory herbicidal effect can be achieved at asmaller dose than a dose by a single use of each agent. Also, theherbicidal composition prepared by combining at least two agrochemicalagents is safe to rice, wheat, barley, corn, grain sorghum, soybeans,cotton, sugar beet, turf, fruit trees and the like, and achieves asatisfactory herbicidal effect by one treatment. The present inventionhas been accomplished on the basis of this discovery.

The present invention is characterized by having the following features.

1. A herbicidal composition which comprises i) an isoxazoline derivativerepresented by the following general formula (I) or its salt and ii) atleast one compound selected from the following Group A:i) Formula (I)

wherein R¹ and R² are respectively independently a hydrogen atom, a C1to C10 alkyl group, a C3 to C8 cycloalkyl group or a C3 to C8 cycloalkylC1 to C3 alkyl group; or R¹ and R² may be bonded to each other to form aC3 to C7 spiro ring together with the carbon atoms to which they bond;

-   -   R³ and R⁴ are respectively independently a hydrogen atom, a C1        to C10 alkyl group or a C3 to C8 cycloalkyl group; or R³ and R⁴        may be bonded to each other to form a C3 to C7 spiro ring        together with the carbon atoms to which they bond; or R¹, R², R³        and R⁴ may form a 5- to 8-membered ring together with the carbon        atoms to which they bond;    -   R⁵ and R⁶ are respectively independently a hydrogen atom or a C1        to C10 alkyl group;    -   Y is a 5- to 6-membered aromatic heterocyclic group or condensed        aromatic heterocyclic group having one or more hetero atoms        selected from a nitrogen atom, an oxygen atom and a sulfur atom;        the heterocyclic group may be substituted with 0 to 6 same or        different groups selected from the following substituent group        α; when the heterocyclic group is substituted at the two        adjacent positions with two alkyl groups, two alkoxy groups, an        alkyl group and an alkoxy group, an alkyl group and an alkylthio        group, an alkyl group and an alkylsulfonyl group, an alkyl group        and a monoalkylamino group, or an alkyl group and a dialkylamino        group, all selected from the substituent group a, the two groups        may form, together with the atoms to which they bond, a 5- to        8-membered ring which may be substituted with 1 to 4 halogen        atoms; the hetero atom of the heterocyclic group, when it is a        nitrogen atom, may be oxidized to become N-oxide;    -   n is an integer of 0 to 2;        (Substituent Group α)

Hydroxyl group; thiol group; halogen atoms; C1 to C10 alkyl groups; C1to C10 alkyl groups each mono-substituted with a group selected from thefollowing substituent group β, C1 to C4 haloalkyl groups; C3 to C8cycloalkyl groups; C1 to C10 alkoxy groups; C1 to C10 alkoxy groups eachmono-substituted with a group selected from the following substituentgroup γ; C1 to C4 haloalkoxy groups; C3 to C8 cycloalkyloxy groups; C3to C8 cycloalkyl C1 to C3 alkyloxy groups; C1 to C10 alkylthio groups;C1 to C10 alkylthio groups each mono-substituted with a group selectedfrom the substituent group γ; C1 to C4 haloalkylthio groups; C2 to C6alkenyl groups; C2 to C6 alkenyloxy groups; C2 to C6 alkynyl groups; C2to C6 alkynyloxy groups; C1 to C10 alkylsulfinyl groups; C1 to C10alkylsulfinyl groups each mono-substituted with a group selected fromthe substituent group γ; C1 to C10 alkylsulfonyl groups; C1 to C10alkylsulfonyl groups each mono-substituted with a group selected fromthe substituent group γ; C1 to C4 haloalkylsulfinyl groups; C1 to C10alkylsulfonyloxy groups each mono-substituted with a group selected fromthe substituent group γ; C1 to C4 haloalkylsulfonyl groups; C1 to C10alkylsulfonyloxy groups; C1 to C4 haloalkylsulfonyloxy groups;optionally substituted phenyl group; optionally substituted phenoxygroup; optionally substituted phenylthio group; optionally substitutedaromatic heterocyclic groups; optionally substituted aromaticheterocyclic oxy groups; optionally substituted aromatic heterocyclicthio groups; optionally substituted phenylsulfinyl groups; optionallysubstituted phenylsulfonyl groups; optionally substituted aromaticheterocyclic sulfonyl groups; optionally substituted phenylsulfonyloxygroups; acyl groups; C1 to C4 haloalkylcarbonyl groups; optionallysubstituted benzylcarbonyl group; optionally substituted benzoyl group;carboxyl group; C1 to C10 alkoxycarbonyl groups; optionally substitutedbenzyloxycarbonyl group; optionally substituted phenoxycarbonyl group;cyano group; carbamoyl group (its nitrogen atom may be substituted withsame or different groups selected from C1 to C10 alkyl groups andoptionally substituted phenyl group); C1 to C6 acyloxy groups; C1 to C4haloalkylcarbonyloxy groups; optionally substituted benzylcarbonyloxygroup; optionally substituted benzoyloxy group; nitro group; and aminogroup (its nitrogen atom may be substituted with same or differentgroups selected from C1 to C10 alkyl groups, optionally substitutedphenyl group, C1 to C6 acyl groups, C1 to C4 haloalkylcarbonyl groups,optionally substituted benzylcarbonyl group, optionally substitutedbenzoyl group, C1 to C10 alkylsulfonyl group, C1 to C4 haloalkylsulfonylgroups, optionally substituted benzylsulfonyl group, and optionallysubstituted phenylsulfonyl group);

(Substituent Group β)

Hydroxyl group; C3 to C8 cycloalkyl groups (which may be substitutedwith halogen atom or alkyl group); C1 to C10 alkoxy groups; C1 to C10alkylthio groups; C1 to C10 alkylsulfonyl groups; C1 to C10alkoxycarbonyl groups; C2 to C6 haloalkenyl groups; amino group (itsnitrogen atom may be substituted with same or different groups selectedfrom C1 to C10 alkyl groups, C1 to C6 acyl groups; C1 to C4haloalkylcarbonyl groups, C1 to C10 alkylsulfonyl groups and C1 to C4haloalkylsulfonyl groups); carbamoyl group (its nitrogen atom may besubstituted with same or different C1 to C10 alkyl groups); C1 to C6acyl groups; C1 to C4 haloalkylcarbonyl groups; C1 to C10 alkoxyiminogroups; cyano group; optionally substituted phenyl group; and optionallysubstituted phenoxy group;

(Substituent Group γ)

C1 to C10 alkoxycarbonyl groups; optionally substituted phenyl group;optionally substituted aromatic heterocyclic groups; cyano group; andcarbamoyl group (its nitrogen atom may be substituted with same ordifferent C1 to C10 alkyl groups); and

ii) Group A

atrazine, simazine, cyanazine, isoxaflutole, mesotrione, flumetsulam,imazethapyr, imazapyr, dicamba, clopyralid, prosulfuron,halosulfuron-methyl, rimsulfuron, bentazone, carfentrazone-ethyl,metribuzin, thifensulfuron-methyl, nicosulfuron, primisulfuron,cloransulam-methyl, glufosinate, glyphosate, glyphosate-trimesium,pendimethalin, linuron, prometryn, diflufenican, flumioxazin, andmetolachlor.

2. The herbicidal composition according to Feature 1, wherein theisoxazoline derivative of the formula (I) or its salt has a substituentselected from the substituent group α on the heterocycle which may besubstituted with 0 to 6 same or different groups, including hydroxylgroup; halogen atoms; C1 to C10 alkyl groups; C1 to C10 alkyl groupseach mono-substituted with a group selected from the substituent groupβ, C1 to C4 haloalkyl groups; C3 to C8 cycloalkyl groups; C1 to C10alkoxy groups; C1 to C10 alkoxy groups each mono-substituted with agroup selected from the substituent group γ; C1 to C4 haloalkoxy groups;C3 to C8 cycloalkyloxy groups; C3 to C8 cycloalkyl C1 to C3 alkyloxygroups; C1 to C10 alkylthio groups; C1 to C10 alkylthio groups eachmono-substituted with a group selected from the substituent group γ; C1to C4 haloalkylthio groups; C2 to C6 alkenyl groups; C2 to C6 alkenyloxygroups; C2 to C6 alkynyl groups; C2 to C6 alkynyloxy groups; C1 to C10alkylsulfonyl groups; C1 to C4 haloalkylsulfonyl groups; optionallysubstituted phenyl group; optionally substituted phenoxy group;optionally substituted phenylthio group; optionally substituted aromaticheterocyclic groups; optionally substituted aromatic heterocyclic oxygroups; optionally substituted aromatic heterocyclic thio groups;optionally substituted phenylsulfonyl groups; optionally substitutedaromatic heterocyclic sulfonyl groups; C1 to C6 acyl groups; C1 to C4haloalkylcarbonyl groups; optionally substituted benzylcarbonyl group;optionally substituted benzoyl group; carboxyl group; C1 to C10alkoxycarbonyl groups; cyano group; carbamoyl group (its nitrogen atommay be substituted with same or different groups selected from C1 to C10alkyl groups and optionally substituted phenyl group); nitro group; andamino group (its nitrogen atom may be substituted with same or differentgroups selected from C1 to C10 alkyl groups, optionally substitutedphenyl group, C1 to C6 acyl groups, C1 to C4 haloalkylcarbonyl groups,optionally substituted benzylcarbonyl group, optionally substitutedbenzoyl group, C1 to C10 alkylsulfonyl groups, C1 to C4haloalkylsulfonyl groups, optionally substituted benzylsulfonyl group,and optionally substituted phenylsulfonyl group); when the heterocyclicgroup is substituted at the two adjacent positions with two alkylgroups, two alkoxy groups, an alkyl group and an alkoxy group, an alkylgroup and an alkylthio group, an alkyl group and an alkylsulfonyl group,an alkyl group and a monoalkylamino group, or an alkyl group and adialkylamino group, the two groups may form, together with the atoms towhich they bond, a 5- to 8-membered ring which may be substituted with 1to 4 halogen atoms.

3. The herbicidal composition according to Feature 2, wherein theisoxazoline derivative of the formula (I) or its salt has a substituentselected from the substituent group α on the heterocycle which may besubstituted with 0 to 6 same or different groups, including halogenatoms; C1 to C10 alkyl groups; C1 to C4 haloalkyl groups; C1 to C10alkoxy C1 to C3 alkyl groups; C3 to C8 cycloalkyl groups (which may besubstituted with halogen atom or alkyl group); C1 to C10 alkoxy groups;C1 to C4 haloalkoxy groups; C3 to C8 cycloalkyl C1 to C3 alkyloxygroups; optionally substituted phenoxy group; C1 to C10 alkylthiogroups; C1 to C10 alkylsulfonyl groups; acyl groups; C1 to C4haloalkylcarbonyl groups; C1 to C10 alkoxycarbonyl groups; cyano groupand carbamoyl group (its nitrogen atom may be substituted with same ordifferent C1 to C10 alkyl groups).

4. The herbicidal composition according to any of Feature 1, 2 or 3,wherein R¹ and R² may be the same or different and are each a methylgroup or an ethyl group; and R³, R⁴, R⁵ and R⁶ are each a hydrogen atom.

5. The herbicidal composition according to any of Feature 1, 2, 3 or 4,wherein Y is a 5- or 6-membered aromatic heterocyclic group having ahetero atom selected from a nitrogen atom, an oxygen atom and a sulfuratom.

6. The herbicidal composition according to Feature 5, wherein Y is athienyl group, a pyrazolyl group, an isoxazolyl group, an isothiazolylgroup, a pyridyl group or a pyrimidinyl group.

7. The herbicidal composition according to Feature 6, wherein Y is athiophen-3-yl group, a pyrazol-4-yl group, a pyrazol-5-yl group, anisoxazol-4-yl group, an isothiazol-4-yl group, a pyridyn-3-yl group or apyrimidin-5-yl group.

8. The herbicidal composition according to Feature 7, wherein Y is athiophen-3-yl group and the thiophene ring is substituted with thesubstituent group α at the 2- and 4-positions.

9. The herbicidal composition according to Feature 7, wherein Y is apyrazol-4-yl group and the pyrazole ring is substituted at the 3- and5-positions with the substituent group α and at the 1-position with ahydrogen atom, a C1 to C10 alkyl group, a C1 to C10 alkyl groupmono-substituted with a group selected from the substituent group β, aC1 to C4 haloalkyl group, a C3 to C8 cycloalkyl group, a C2 to C6alkenyl group, a C2 to C6 alkynyl group, a C1 to C10 alkylsulfinylgroup, a C1 to C10 alkylsulfonyl group, a C1 to C10 alkylsulfonyl groupmono-substituted with a group selected from the substituent group γ, aC1 to C4 haloalkylsulfonyl group, an optionally substituted phenylgroup, an optionally substituted aromatic heterocyclic group, anoptionally substituted phenylsulfonyl group, an optionally substitutedaromatic heterocyclic sulfonyl group, an acyl group, a C1 to C4haloalkylcarbonyl group, an optionally substituted benzylcarbonyl group,an optionally substituted benzoyl group, a C1 to C10 alkoxycarbonylgroup, an optionally substituted benzyloxycarbonyl group, an optionallysubstituted phenoxycarbonyl group, a carbamoyl group (its nitrogen atommay be substituted with same or different groups selected from C1 to C10alkyl groups and optionally substituted phenyl group), or an amino group(its nitrogen atom may be substituted with same or different groupsselected from C1 to C10 alkyl groups, an optionally substituted phenylgroup, acyl groups, C1 to C4 haloalkylcarbonyl groups, an optionallysubstituted benzylcarbonyl group, an optionally substituted benzoylgroup, C1 to C10 alkylsulfonyl groups, C1 to C4 haloalkylsulfonylgroups, an optionally substituted benzylsulfonyl group and an optionallysubstituted phenylsulfonyl group).

10. The herbicidal composition according to Feature 7, wherein Y is apyrazol-5-yl group and the pyrazole ring is substituted at the4-position with the substituent group α and at the 1-position with ahydrogen atom, a C1 to C10 alkyl group, a C1 to C10 alkyl groupmono-substituted with a group selected from the substituent group β, aC1 to C4 haloalkyl group, a C3 to C8 cycloalkyl group, a C2 to C6alkenyl group, a C2 to C6 alkynyl group, a C1 to C10 alkylsulfinylgroup, a C1 to C10 alkylsulfonyl group, a C1 to C10 alkylsulfonyl groupmono-substituted with a group selected from the substituent group γ, aC1 to C4 haloalkylsulfonyl group, an optionally substituted phenylgroup, an optionally substituted aromatic heterocyclic group, anoptionally substituted phenylsulfonyl group, an optionally substitutedaromatic heterocyclic sulfonyl group, an acyl group, a C1 to C4haloalkylcarbonyl group, an optionally substituted benzylcarbonyl group,an optionally substituted benzoyl group, a C1 to C10 alkoxycarbonylgroup, an optionally substituted benzyloxycarbonyl group, an optionallysubstituted phenoxycarbonyl group, a carbamoyl group (its nitrogen atommay be substituted with same or different groups selected from C1 to C10alkyl groups and an optionally substituted phenyl group), or an aminogroup (its nitrogen atom may be substituted with same or differentgroups selected from C1 to C10 alkyl groups, an optionally substitutedphenyl group, acyl groups, C1 to C4 haloalkylcarbonyl groups, anoptionally substituted benzylcarbonyl group, an optionally substitutedbenzoyl group, C1 to C10 alkylsulfonyl groups, C1 to C4haloalkylsulfonyl groups, an optionally substituted benzylsulfonyl groupand an optionally substituted phenylsulfonyl group).

11. The herbicidal composition according to Feature 7, wherein Y is anisoxazol-4-yl group and the isoxazole ring is substituted with thesubstituent group α at the 3- and 5-positions.

12. The herbicidal composition according to Feature 7, wherein Y is anisothiazol-4-yl group and the isothiazole ring is substituted with thesubstituent group α at the 3- and 5-positions.

13. The herbicidal composition according to Feature 7, wherein Y is apyridin-3-yl group and the pyridine ring is substituted with thesubstituent group α at the 2- and 4-positions.

14. The herbicidal composition according to Feature 7, wherein Y is apyrimidin-5-yl group and the pyrimidine ring is substituted with thesubstituent group α at the 4- and 6-positions.

15. The herbicidal composition according to any of Features 1 to 14,wherein n is an integer of 2.

16. The herbicidal composition according to any of Features 1 to 14,wherein the compound of Group A is at least one compound selected fromthe group consisting of atrazine, cyanazine, simazine and prometryn.

17. The herbicidal composition according to any of Features 1 to 14,wherein the compound of Group A is at least one compound selected fromthe group consisting of glyphosate, glufosinate, linuron andflumetsulam.

18. A herbicidal composition which comprises i) the isoxazolinederivative or its salt is a compound as defined in Feature 9 and ii) thecompound of Group A is at least one compound selected from the groupconsisting of atrazine, cyanazine, simazine, prometryn, glyphosate,glufosinate, linuron, flumetsulam, metribuzin, isoxaflutole, mesotrione,diflufenican, pendimethalin and flumioxazin.

19. A herbicidal composition which comprises i) the isoxazolinederivative or its salt is a compound as defined in Feature 9 and ii) thecompound of Group A is at least one compound selected from the groupconsisting of atrazine, cyanazine, simazine and prometryn.

20. A herbicidal composition which comprises i) the isoxazolinederivative or its salt is a compound as defined in Feature 9 and ii) thecompound of Group A is at least one compound selected from the groupconsisting of glyphosate, glufosinate, linuron and flumetsulam.

21. The herbicidal composition according to any of Features 1 to 20,wherein ii) at least one compound of Group A is contained in an amountof from 0.001 to 100 parts by weight to 1 part by weight of i) anisoxazoline derivative represented by the Formula (I) or its salt.

22. The herbicidal composition according to any of Features 1 to 21,which is used as an agrochemical product containing i) an isoxazolinederivative of the Formula (I) or its salt and ii) at least one compoundof Group A in a total amount of from 0.5 to 90 wt %.

The definitions of the terms used in the present specification are givenbelow.

The expression of “C1 to C10”, etc. indicates that the substituentappearing after the expression has 1 to 10 carbon atoms in the case of“C1 to C10”.

Halogen atom refers to a fluorine atom, a chlorine atom, a bromine atomor an iodine atom.

C1 to C10 alkyl group refers to a straight or branched chain alkyl groupof 1 to 10 carbon atoms unless other wise specified; and there can bementioned, for example, methyl group, ethyl group, n-propyl group,isopropyl group, n-butyl group, isobutyl group, sec-butyl group,tert-butyl group, n-pentyl group, isopentyl group, neopentyl group,n-hexyl group, isohexyl group, 3,3-dimethylbutyl group, heptyl group andoctyl group.

C3 to C8 cycloalkyl group refers to a cycloalkyl group of 3 to 8 carbonatoms; and there can be mentioned, for example, cyclopropyl group,cyclobutyl group, cyclopentyl group and cyclohexyl group.

C3 to C8 cycloalkyl C1 to C3 alkyl group (which may be substituted withhalogen atom or alkyl group) refers, unless otherwise specified, to a C1to C3 alkyl group substituted with a C3 to C8 cycloalkyl group which maybe substituted with 1 to 4 same or different halogen atoms or C1 to C3alkyl group; and there can be mentioned, for example, cyclopropylmethylgroup, 1-cyclopropylethyl group, 2-cyclopropylethyl group,1-cyclopropylpropyl group, 2-cyclopropylpropyl group,3-cyclopropylpropyl group, cyclobutylmethyl group, cyclopentylmethylgroup, cyclohexylmethyl group, 2-chlorocyclopropylmethyl group,2,2-dichlorocyclopropylmethyl group, 2-fluorocyclopropylmethyl group,2,2-difluorocyclopropylmethyl group, 2-methylcyclopropylmethyl group,2,2-dimethylcyclopropylmethyl group and 2-methylcyclopropylethyl group.

C3 to C8 cycloalkyl C1 to C3 alkyl group refers to a alkyl group of 1 to3 carbon atoms, substituted with a cycloalkyl group of 3 to 8 carbonatoms; and there can be mentioned, for example, cyclopropylmethyl group,1-cyclopropylethyl group, 2-cyclopropylethyl group, 1-cyclopropylpropylgroup, 2-cyclopropylpropyl group, 3-cyclopropylpropyl group,cyclobutylmethyl group, cyclopentylmethyl group and cyclohexylmethylgroup.

C1 to C4 haloalkyl group refers, unless otherwise specified, to astraight or branched chain alkyl group of 1 to 4 carbon atoms,substituted with 1 to 9 same or different halogen atoms; and there canbe mentioned, for example, fluoromethyl group, chloromethyl group,bromomethyl group, difluoromethyl group, trifluoromethyl group,2,2-difluoroethyl group, 2,2,2-trifluoroethyl group and pentafluoroethylgroup.

C2 to C6 alkenyl group refers to a straight or branched chain alkenylgroup of 2 to 6 carbon atoms; and there can be mentioned, for example,ethenyl group, 1-propenyl group, 2-propenyl group, isopropenyl group,1-butenyl group, 2-butenyl group, 3-butenyl group and 2-pentenyl group.

C2 to C6 alkynyl group refers to a straight or branched chain alkynylgroup of 2 to 6 carbon atoms; and there can be mentioned, for example,ethynyl group, 2-propynyl group, 1-methyl-2-propynyl group, 2-butynylgroup, 3-butynyl group and 2-methyl-3-butynyl group.

C2 to C6 haloalkenyl group refers, unless otherwise specified, to astraight or branched alkenyl group of 2 to 6 carbon atoms, substitutedwith 1 to 4 same or different halogen atoms; and there can be mentioned,for example, 3-chloro-2-propenyl group and 2-chloro-2-propenyl group.

C1 to C10 alkoxy group refers to an (alkyl)-O— group wherein the alkylmoiety has the above definition; and there can be mentioned, forexample, methoxy group, ethoxy group, n-propoxy group, isopropoxy group,tert-butoxy group, n-butoxy group, sec-butoxy group and isobutoxy group.

C1 to C4 haloalkoxy group refers to a (haloalkyl)-O— group wherein thehaloalkyl moiety has the above definition; and there can be mentioned,for example, difluoromethoxy group, trifluoromethoxy group,2,2-difluoroethoxy group and 2,2,2-trifluoroethoxy group.

C3 to C8 cycloalkyloxy group refers to a (cycloalkyl)-O— group whereinthe cycloalkyl moiety has the above definition; and there can bementioned, for example, cyclopropyloxy group, cyclobutyloxy group,cyclopentyloxy group and cyclohexyloxy group.

C3 to C8 cycloalkyl C1 to C3 alkyloxy group refers to a(cycloalkylalkyl)-O— group wherein the cycloalkylalkyl moiety has theabove definition; and there can be mentioned, for example,cyclopropylmethoxy group, 1-cyclopropylethoxy group, 2-cyclopropylethoxygroup, 1-cyclopropylpropoxy group, 2-chclopropylpropoxy group,3-cyclopropylpropoxy group, cyclobutylmethoxy group, cyclopentylmethoxygroup and cyclohexylmethoxy group.

C2 to C6 alkenyloxy group and C2 to C6 alkynyloxy group refer,respectively, to an (alkenyl)-O— group and an (alkynyl)-O— group, ineach of which the alkenyl or alkynyl moiety has the above definition;and there can be mentioned, for example, 2-propenyloxy group and2-propynyloxy group.

C1 to C10 alkoxyimino group refers to an (alkoxy)-N═ group wherein thealkoxy moiety has the above definition; and there can be mentioned, forexample, methoxyimino group and ethoxyimino group.

C1 to C10 alkylthio group, C1 to C10 alkylsulfinyl group and C1 to C10alkylsulfonyl group refer, respectively, to an (alkyl)-S— group, an(alkyl)-SO— group and an (alkyl)-SO₂— group, in each of which the alkylmoiety has the above definition; and there can be mentioned, forexample, methylthio group, ethylthio group, n-propylthio group,isopropylthio group, methylsulfinyl group, methylsulfonyl group,ethylsulfonyl group, n-propylsulfonyl group and isopropylsulfonyl group.

C1 to C10 alkylsulfonyloxy group refers to an (alkylsulfonyl)-O— groupwherein the alkylsulfonyl moiety has the above definition, and there canbe mentioned, for example, methylsulfonyloxy group and ethylsulfonyloxygroup.

C1 to C10 alkoxycarbonyl group refers to an (alkoxy)-CO— group whereinthe alkoxy moiety has the above definition, and there can be mentioned,for example, methoxycarbonyl group, ethoxycarbonyl group,n-propoxycarbonyl group and isopropoxycarbonyl group.

C1 to C6 acryl group refers to a straight or branched chain aliphaticacyl group of 1 to 6 carbon atoms, and there can be mentioned, forexample, formyl group, acetyl group, propionyl group, isopropionylgroup, butyryl group and pivaloyl group.

C1 to C10 acyloxy group refers to an (acyl)-O— group wherein the acylmoiety has the above definition; and there can be mentioned, forexample, acetoxy group, propionyloxy group, ispropionyloxy group andpivalolyoxy group.

C1 to C4 haloalkylcarbonyl group, C1 to C4 haloalkylthio group and C1 toC4 haloalkylsulfonyl group refers, respectively, to a (haloalkyl)-CO—group, a (haloalkyl)-S— group and a (haloalkyl)-SO₂— group, in each ofwhich the haloalkyl moiety has the above definition; and there can bementioned, for example, chloroacetyl group, trifluoroacetyl group,pentafluoropropyl group, difluoromethylthio group, trifluoromethylthiogroup, chloromethylsulfonyl group, difluoromethylsulfonyl group andtrifluoromethylsulfonyl group.

C1 to C4 haloalkylcarbonyloxy group and C1 to C4 haloalkylsulfonyloxygroup refer, respectively, to a (haloalkylcarbonyl)-O— group and a(haloalkylsulfonyl)-O— group, in each of which the haloalkylcarbonylmoiety or the haloalkylsulfonyl moiety has the above definition; andthere can be mentioned, for example, chloroacetyloxy group,trifluoroacetyloxy group, chloromethylsulfonyloxy group andtrifluoromehtylsulfonyloxy group.

“Optionally substituted” in (optionally substituted) phenyl group,(optionally substituted) aromatic heterocyclic group, (optionallysubstituted) phenoxy group, (optionally substituted aromaticheterocyclic oxy group, (optionally substituted) phenylthio group,(optionally substituted) aromatic heterocyclic thio group, (optionallysubstituted) phenylsulfonyl group, (optionally substituted)phenylsulfonyloxy group, (optionally substituted) aromatic heterocyclicsulfonyl group, (optionally substituted) benzylcarbonyl group,(optionally substituted) benzylcarbonyloxy group, (optionallysubstituted) benzylsulfonyl group, (optionally substituted) benzoylgroup, (optionally substituted) benzoyloxy group, (optionallysubstituted) benzyloxycarbonyl group and (optionally substituted)phenoxycarbonyl group, refers to being optionally substituted with, forexample, halogen atom, C1 to C10 alkyl group, C1 to C4 haloalkyl group,C1 to C10 alkoxyalkyl group, C1 to C10 alkoxy group, C1 to C10 alkylthiogroup, C1 to C10 alkylsulfonyl group, acyl group, C1 to C10alkoxycarbonyl group, cyano group, carbamoyl group (its nitrogen atommay be substituted with same or different C1 to C10 alkyl groups), nitrogroup or amino group (its nitrogen atom may be substituted with same ordifferent groups selected from C1 to C10 alkyl groups, C1 to C6 acylgroups, C1 to C4 haloalkylcarbonyl groups, C1 to C10 alkylsulfonylgroups and C1 to C4 haloalkylsulfonyl groups).

5- to 6-membered aromatic heterocyclic group having a hetero atomselected from a nitrogen atom, an oxygen atom and a sulfur atomincludes, for example, furyl group, thienyl group, pyrrolyl group,pyrazolyl group, isoxazolyl group, isothiazolyl group, oxazolyl group,thiazolyl group, imidazolyl group, pyridyl group, pyridazinyl group,pyrimidinyl group, pyrazinyl group, triazinyl group, triazolyl group,oxadiazolyl group and thiadiazolyl group, each having 1 to 3 heteroatoms.

Fused aromatic heterocyclic group refers to a group having 1 to 3 heteroatoms randomly selected from nitrogen atom, oxygen atom and sulfur atom;and there can be mentioned, for example, benzofuryl group, benzothienylgroup, indolyl group, benzoxazolyl group, benzothiazolyl group,benzimidazolyl group, benzisoxazolyl group, benzisothiazolyl group,indazolyl group, quinolyl group, isoquinolyl group, phthalazinyl group,quinoxalinyl group, quinazolinyl group, cinnolinyl group andbenzotriazolyl group.

Aromatic heterocycle in (optionally substituted) aromatic heterocyclicgroup, (optionally substituted) aromatic heterocyclic oxy group,(optionally substituted) aromatic heterocyclic thio group and(optionally substituted) aromatic heterocyclic sulfonyl group, refers toa 5- to 6-membered group having 1 to 3 hetero atoms randomly selectedfrom nitrogen atom, oxygen atom and sulfur atom; and there can bementioned, for example, furyl group, thienyl group, pyrrolyl group,pyrazolyl group, isoxazolyl group, isothiazolyl group, oxazolyl group,thiazolyl group, imidazolyl group, pyridyl group, pyridazinyl group,pyrimidinyl group, pyrazinyl group, triazinyl group, triazolyl group,oxadiazolyl group and thiadiazolyl group.

Pharmaceutically acceptable salt is a salt of a compound of the generalformula [I] having, in the structure, hydroxyl group, carboxyl group,amino group or the like, with a metal or an organic base or with amineral acid or an organic acid. As the metal, there can be mentionedalkali metals such as sodium, potassium and the like; and alkaline earthmetals such as magnesium, calcium and the like. As the organic base,there can be mentioned triethylamine, diisopropylamine, etc. As themineral acids, there can be mentioned hydrochloric acid, sulfuric acid,etc. As the organic acid, there can be mentioned acetic acid,methanesulfonic acid, p-toluenesulfonic acid, etc.

In the above-mentioned general formula [I], it is preferred that

-   -   R¹ and R² may be the same or different and are each a methyl        group or an ethyl group;    -   R³, R⁴, R⁵ and R⁶ are each a hydrogen atom;    -   n is an integer of 2; and    -   Y is a thiophen-3-yl group [the 2- and 4-positions of the group        are substituted with same or different groups selected from        halogen atoms, alkyl groups, haloalkyl groups, alkoxyalkyl        groups, cycloalkyl groups, alkoxy groups, haloalkoxy groups,        acyl groups, haloalkylcarbonyl groups, alkoxycarbonyl groups,        cyano group and carbamoyl group (its nitrogen atom may be        substituted with same or different alkyl groups)], or    -   a pyrazol-4-yl group [the 3- and 5-positions of the group are        substituted with same or different groups selected from halogen        atoms, alkyl groups, haloalkyl groups, alkoxyalkyl groups,        cycloalkyl groups, alkoxy groups, haloalkoxy groups,        cycloalkylalkyloxy groups, optionally substituted phenoxy group,        alkylthio groups, alkylsulfonyl groups, acyl groups,        haloalkylcarbonyl groups, alkoxycarbonyl groups, cyano group and        carbamoyl group (its nitrogen atom may be substituted with same        or different alkyl groups); the 1-position is substituted with        hydrogen atom, alkyl group, alkyl group mono-substituted with a        group selected from the substituent group β, haloalkyl group,        cycloalkyl group, alkenyl group, alkynyl group, alkylsulfonyl        group, alkylsulfonyl group mono-substituted with a group        selected from the substituent group γ, haloalkylsulfonyl group,        optionally substituted phenyl group, optionally substituted        aromatic heterocyclic group, optionally substituted        phenylsulfonyl group, optionally substituted aromatic        heterocyclicsulfonyl group, acyl group, haloalkylcarbonyl group,        optionally substituted benzylcarbonyl group, optionally        substituted benzoyl group, alkoxycarbonyl group, optionally        substituted benzyloxycarbonyl group, optionally substituted        phenoxycarbonyl group or carbamoyl group (its nitrogen atom may        be substituted with same or different groups selected from alkyl        groups and optionally substituted phenyl group)], or    -   a pyrazol-5-yl group [the 4-position of the group is substituted        with halogen atom, alkyl group, haloalkyl group, alkoxyalkyl        group, haloalkoxy group, acyl group, haloalkylcarbonyl group,        alkoxycarbonyl group, cyano group or carbamoyl group (its        nitrogen atom maybe substituted with same or different alkyl        groups); the 1-position is substituted with hydrogen atom, alkyl        group, alkyl group mono-substituted with a group selected from        the substituent group β, haloalkyl group, cycloalkyl group, or        optionally substituted phenyl group], or    -   an isoxazol-4-yl group [the 3- and 5-positions of the group are        substituted with same or different groups selected from halogen        atoms, alkyl groups, haloalkyl groups, alkoxyalkyl groups,        cycloalkyl groups, alkoxy groups, haloalkoxy groups, alkylthio        groups, alkylsulfonyl groups, acyl groups, haloalkylcarbonyl        groups, alkoxycarbonyl groups, cyano group and carbamoyl group        (its nitrogen atom may be substituted with same or different        alkyl groups)], or    -   an isothiazol-4-yl group [the 3- and 5-positions of the group        are substituted with same or different groups selected from        halogen atoms, alkyl groups, haloalkyl groups, alkoxyalkyl        groups, cycloalkyl groups, alkoxy groups, haloalkoxy groups,        optionally substituted phenoxy group, alkylthio groups,        alkylsulfonyl groups, acyl groups, haloalkylcarbonyl groups,        alkoxycarbonyl groups, cyano group and carbamoyl group (its        nitrogen atom may be substituted with same or different alkyl        groups)], or    -   a pyridin-3-yl group [the 2- and 4-positions of the group are        substituted with same or different groups selected from halogen        atoms, alkyl groups, haloalkyl groups, alkoxyalkyl groups,        cycloalkyl groups, alkoxy groups, haloalkoxy groups, alkylthio        groups, alkylsulfonyl groups, acyl groups, haloalkylcarbonyl        groups, alkoxycarbonyl groups, cyano group and carbamoyl group        (its nitrogen atom may be substituted with same or different        alkyl groups)], or    -   a pyrimidin-5-yl group [the 4- and 6-positions of the group are        substituted with same or different groups selected from halogen        atoms, alkyl groups, haloalkyl groups, alkoxyalkyl groups,        cycloalkyl groups, alkoxy groups, haloalkoxy groups, alkylthio        groups, alkylsulfonyl groups, acyl groups, haloalkylcarbonyl        groups, alkoxycarbonyl groups, cyano group and carbamoyl group        (its nitrogen atom may be substituted with same or different        alkyl groups)].

BEST MODE FOR CARRYING OUT THE INVENTION

Although it depends on relative activities of respective ingredients,the composition of the present invention contains at least one compoundof the formula (I) generally in an amount of from 0.001 to 100 parts byweight, preferably from 0.01 to 50 parts by weight, more preferably from0.05 to 30 parts by weight to 1 part by weight of an isoxazolinederivative of the formula (I) or its salt.

One active ingredient in the composition of the present invention is acompound of the formula (I), and achieves an excellent herbicidal effectby itself.

Particularly, it does not have a substantial phytotoxicity to rice,wheat, barley, corn, grain sorghum, soybeans, cotton, sugar beet, turf,fruit trees and the like, but achieves an excellent herbicidal effect ata small dose to various weeds growing on an upland field in a wide termrange of from before germination to growing season, such as gramineousweeds including barnyardgrass (Echinochloa crusglli var. crus-galli),crabgrass (Digitaria ciliaris), green foxtail (Setaria viridis), annualbluegrass (Poa annua), johnsongrass (Sorghum halepense Pers.),blackgrass (Alopecurus myosuroides), wild oats (Avena fatua), and thelike, broad leaf weeds including pale persicaria (Polygonumlapathifolia), slender amaranth (Amaranthus viridis), commonlambsquarters (Chenopodium album L.), common chickweed (Stellaria mediaVillars), velvetleaf (Abutilon theophrasti Medic), prickly sida (Sidaspinosa L.), Hemp sesbania (Sesbania exaltata Cory), common ragweed(Ambrosia artemisiifolia), morningglory, and the like, and annual andperennial sedge weeds including purple nutsedge (Cyperus rotundus L.),yellow nutsedge (Cyperus esculentus L.), hime-kugu (Cyperus brevifoliusH.), sedge weed (Cyperus microiria Steud), rice flatsedge (Cyperus iriaL.), and the like.

Further, the. composition of the present invention achieves an excellentherbicidal effect at a small dose to various weeds growing on a paddyfield in a wide term range of from before germination to growing season,such as annual weeds including watergrass (Echinochloa oryzicola),smallflower umbrella plant (Cyperus difformis), konagi (Monochoriavaginalis), aze-na (Lindernia procumbens) and the like, and perennialweeds including mizu-gayatsuri (Cyperus serotinus), kuroguwai(Eleocharis kuroguwai), inu-hotaru-i (Scirpus juncoides), and the like.

A compound of the following Group A which is another active ingredientto be used in combination with an isoxazoline derivative of the formula(I) or its salt, has less phytotoxicity to gramineous crops such as cornwheat and the like, but has a herbicidal activity to only a part ofgramineous weeds such as green foxtail and broad leaf weeds such asbarnyardgrass, common lambsquarters and velvetleaf, and its herbicidalspectrum is narrow.

Group A

atrazine, simazine, cyanazine, isoxaflutole, mesotrione, flumetsulam,imazethapyr, imazapyr, dicamba, clopyralid, prosulfuron,halosulfuron-methyl, rimsulfuron, bentazone, carfentrazone-ethyl,metribuzin, thifensulfuron-methyl, nicosulfuron, primisulfuron,cloransulam-methyl, glufosinate, glyphosate, glyphosate-trimesium,pendimethalin, linuron, prometryn, diflufenican, flumioxazin, andmetolachlor.

The present invention provides a herbicidal composition effective forapplying to a new cultivation method such as non-tillage cultivation inorder to selectively control a wide range of weeds. The herbicidalcomposition of the present invention is particularly effective forkilling main weeds in a corn field, such as dicotyledons including wildbuckwheat (Fallopia convolvulua A.), sanae-tade (Polygonum scabrum),common purslane (Portulaca oleracea L.), common lambsquarters(Chenopodium album L.), common amaranth (Amaranthus retroflexus L.),wild mustard (Sinapis Arvensis L.), hemp sesbania (Sesbania oxaltataCory), sicklepod (Cassia obtusifolia L.), velvetleaf (Abutilontheophrasti Medic), prickly sida (Sida spinosa L.), ivyleaf morningglory(Ipomoea hederacea Jacq), common morning glory (Ipomoea purpurea),jimsonweek (Datura stramonium), black nightshade (Solanum nigrum L.),common cocklebur (Xanthium strumarium L.), sunflower, field bindweed(Convolvulus arvensis), sun spurge (Euphorbia helioscopia), devilsbeggarticks (Bidens frondosa L.), common ragweed (Ambrosiaartemisiifolia) and the like, and monocotyledons including barnyardgrass(Echinochloa crusglli var. crus-galli), green foxtail (Setaria viridis),giant foxtail (Setari faberi), yellow foxtail (Setari glacuca),crabgrass (Digitaria ciliaris), goosegrass (Eleusine indica Gaertn),johnsongrass (Sorghum halepense Pers.), quackgrass (Agropyron repensP.), shattercane (Sorghum vulgare), and the like, but does not havephytotoxicity to aimed crops such as corn and soybeans which grow aftercorn.

The herbicidal composition of the present invention contains at leastone compound of Group A in an amount of from 0.001 to 100 parts byweight, preferably from 0.01 to 50 parts by weight, more preferably from0.05 to 30 parts by weight to 1 part by weight of an isoxazolinederivative of the formula (I) or its salt. If the amount of a herbicideof Group A is less than 0.001 part by weight, a satisfactory effect cannot be achieved, and if this amount exceeds 100 parts by weight, safetyto aimed crops becomes insufficient.

Among compounds of Group A, at least one compound selected from thegroup consisting of atrazine, cyanazine, simazine and prometryn, or atleast one compound selected from the group consisting of glyphosate,glufosinate, linuron and flumetsulam, is preferable. Particularly,cyanazine or atrazine is preferable.

Next, representative examples of the present compound represented by thegeneral formula (I) are shown in Tables 1 to 14. However, the presentcompound is not restricted to these examples.

The following abbreviated expressions used in the Tables refer to thefollowing groups.

-   -   Me: methyl group Et: ethyl group    -   Pr: n-propyl group Pr-i: isopropyl group    -   Pr-c: cyclopropyl group Bu: n-butyl group    -   Bu-i: isobutyl group Bu-s: sec-butyl group    -   Bu-t: tert-butyl group Bu-c: cyclobutyl group    -   Pen: n-pentyl group Pen-c: cyclopentyl group    -   Hex: n-hexyl group Hex-c: cyclohexyl group    -   Ph: phenyl group

For example, (4-Cl)Ph indicates 4-chlorophenyl group, and 3-Hexindicates 3-hexyl group.

When the present compound contains hydroxyl group as a substituent,there may exist keto-enol tautomers. Any of these tautomers and anymixture of these tautomers are included in the present compound. TABLE 1

Melting point (° C.) or Comp. refractive No. R¹ R² R³ R⁴ n R⁵ R⁶ Z₁ R²²R²³ R²⁴ index (n_(D) ²⁰) 1-0001 Me Me H H 2 H H S Me H H 66-68 1-0002 MeMe H H 2 H H S Cl Me H 87-88 1-0003 Me Me H H 2 H H S H H Me 95-971-0004 Me Me H H 2 H H S Cl H H 70-72 1-0005 Me Me H H 2 H H S H H Cl118-119 1-0006 Me Me H H 2 H H O H H H Unmesurable 1-0007 Me Me H H 2 HH O H H C(═O)OMe 124-125

TABLE 2

Melting point (° C.) or Comp. refractive No. R¹ R² R³ R⁴ n R⁵ R⁶ Z² R²⁵R²⁶ R²⁷ index (n_(D) ²⁰) 2-0001 Me Me H H 2 H H S Me C(═NOMe)Me Me 95-962-0002 Me Me H H 0 H H S Me C(═NOMe)Me Me 2-0003 Me Me H H 2 H H S H H H 99-101 2-0004 Me Me H H 2 H H S H OMe H 96-97 2-0005 Me Me H H 2 H H SCl H Cl 125-127 2-0006 Me Me H H 2 H H S Cl Cl Cl 158-160 2-0007 Me Me HH 2 H H S Me Me Me 117-117 2-0008 Me Me H H 2 H H S Me C(═O)Me Me146-148 2-0009 Me Me H H 2 H H S Ph C(═O)Me Me 1.5730 2-0010 Me Me H H 2H H S Ph C(═NOMe)Me Me 129-131 2-0011 Me Me H H 2 H H S Cl C(═O)OMe Cl157-158 2-0012 Me Me H H 2 H H S Cl C(═O)NHMe Cl 178-180 2-0013 Me Me HH 2 H H O H H H 58-61 2-0014 Me Me H H 2 H H O Me H Cl 180-181

TABLE 3

Melting point (° C.) or Comp. refractive No. R¹ R² R³ R⁴ n R⁵ R⁶ R²⁹ R²⁸R³⁰ index (n_(D) ²⁰) 3-0001 Me Me H H 0 H H CF₃ Ph Cl 89-90 3-0002 Me MeH H 2 H H CF₃ Ph Cl 132-133 3-0003 Me Me H H 1 H H Ph Me Cl Unmesurable3-0004 Me Me H H 2 H H CF₃ Ph SO₂Et 158-160 3-0005 Me Me H H 2 H H CF₃Ph N(Me)₂ 150-151 3-0006 Me Me H H 0 H H CF₃ Bu-t Cl 79-81 3-0007 Me MeH H 0 H H CF₃ H Cl 120-122 3-0008 Me Me H H 0 H H CF₃ CHF₂ Cl 41-423-0009 Me Me H H 0 H H Cl CHF₂ CF₃ 89-90 3-0010 Me Me H H 2 H H CF₃ CHF₂Cl 126-127 3-0011 Me Me H H 2 H H Cl CHF₂ CF₃ 136-137 3-0012 Me Me H H 2H H OEt Me CF₃ 124-125 3-0013 Me Me H H 2 H H CF₃ Me OMe 113-114 3-0014Me Me H H 2 H H CF₃ Me O(2-Cl)Ph 67-70 3-0015 Me Me H H 2 H H CF₃ MeOPen-c 113-114 3-0016 Me Me H H 2 H H CF₃ Me CN 105-108 3-0017 Me Me H H2 H H Cl Et Cl 105-107 3-0018 Me Me H H 2 H H CHF₂ Me Cl 78-79 3-0019 MeMe H H 2 H H CF₃ —(CH₂)₃O— 151-152 3-0020 Me Me H H 0 H H CHF₂ Me Cl1.5183 3-0021 Me Me H H 0 H H CF₃ Ph F 3-0022 Me Me H H 0 H H CF₃ Ph SEt3-0023 Me Me H H 0 H H CF₃ Ph N(Me)2 3-0024 Me Me H H 0 H H OMe Me CF₃3-0025 Me Me H H 0 H H OH Me CF₃ 3-0026 Me Me H H 0 H H OEt Me CF₃3-0027 Me Me H H 0 H H CF₃ Me F 3-0028 Me Me H H 0 H H CF₃ Me OMe 3-0029Me Me H H 0 H H CF₃ Me O(2-Cl)Ph 3-0030 Me Me H H 0 H H CF₃ Me OPen-c3-0031 Me Me H H 0 H H CF₃ Me CN 3-0032 Me Me H H 0 H H Cl Et Cl 3-0033Me Me H H 0 H H CF₃ —(CH₂)₃O— 3-0034 Me Me H H 2 H H CF₃ H Cl 138-140

TABLE 4 Melting point (° C.) or Comp. refractive No. R¹ R² R³ R⁴ n R⁵ R⁶R²⁹ R²⁸ R³⁰ index (n_(D) ²⁰) 3-0035 Me Me H H 2 H H H Me Cl 105-1063-0036 Me Me H H 2 H H Me Me Me 148-150 3-0037 Me Me H H 2 H H Me Me Cl 99-101 3-0038 Me Me H H 2 H H Cl Me Cl 143-145 3-0039 Me Me H H 2 H HCF₃ Me Cl 115-116 3-0040 Me Me H H 2 H H Cl Me CF₃ 120-122 3-0041 Me MeH H 2 H H CF₃ Me F 79-82 3-0042 Me Me H H 2 H H CF₃ Me OH 90-92 3-0043Me Me H H 2 H H OMe Me CF₃ 125-126 3-0044 Me Me H H 2 H H CF₃ Me OEt92-94 3-0045 Me Me H H 2 H H CF₃ Me OPr-i 69-71 3-0046 Me Me H H 2 H HCF₃ Me OPr 82-83 3-0047 Me Me H H 2 H H CF₃ Me OBu-t 86-89 3-0048 Me MeH H 2 H H CF₃ Me OBu 61-62 3-0049 Me Me H H 2 H H CF₃ Me OHex-c 124-1253-0050 Me Me H H 2 H H CF₃ Me OCH₂Pr-c 93-94 3-0051 Me Me H H 2 H H CF₃Me OCH₂Pen-c 112-113 3-0052 Me Me H H 2 H H CF₃ Me OCH₂Hex-c 56-593-0053 Me Me H H 2 H H CF₃ Me OCH₂C≡CH 92-93 3-0054 Me Me H H 2 H H CF₃Me OCHF₂ 129-130 3-0055 Me Me H H 2 H H OCHF₂ Me CF₃ Unmesurable 3-0056Me Me H H 2 H H CF₃ Me OCH₂CHF₂ 89-91 3-0057 Me Me H H 2 H H CF₃ MeOCH₂CF₃ 93-95 3-0058 Me Me H H 2 H H CF₃ Me OCH₂CN 1.4872 3-0059 Me Me HH 2 H H CF₃ Me OCH₂Ph 79-81 3-0060 Me Me H H 2 H H CF₃ Me OPh 122-1233-0061 Me Me H H 2 H H CF₃ Me O(3-Cl)Ph Unmesurable 3-0062 Me Me H H 2 HH CF₃ Me O(3-OMe)Ph 1.5059 3-0063 Me Me H H 2 H H CF₃ Me O(4-Cl)Ph 68-693-0064 Me Me H H 2 H H CF₃ Me O(4-Me)Ph 132-133 3-0065 Me Me H H 2 H HCF₃ Me O(4-OMe)Ph 115-117 3-0066 Me Me H H 2 H H CF₃ Me OC(═O)Me 130-1313-0067 Me Me H H 2 H H CF₃ Me SO₂Me 168-169 3-0068 Me Me H H 2 H H CF₃Me SEt 100-102 3-0069 Me Me H H 2 H H CF₃ Me SO₂Et 107-108 3-0070 Me MeH H 2 H H CF₃ Me SO₂Ph 166-168 3-0071 Me Me H H 2 H H CF₃ Me Me 105-1073-0072 Me Me H H 2 H H Ph Me Cl 127-129 3-0073 Me Me H H 2 H H CF₃ Et Cl111-112

TABLE 5 Melting point (° C.) or Comp. refractive No. R¹ R² R³ R⁴ n R⁵ R⁶R²⁹ R²⁸ R³⁰ index (n_(D) ²⁰) 3-0074 Me Me H H 2 H H Cl Et CF₃ 112-1143-0075 Me Me H H 2 H H CF₃ Pr-i Cl 157-158 3-0076 Me Me H H 2 H H ClPr-i CF₃ 135-136 3-0077 Me Me H H 2 H H CF₃ Pr Cl 89-90 3-0078 Me Me H H2 H H Cl Pr CF₃ 111-113 3-0079 Me Me H H 2 H H CF₃ Bu-t H 101-103 3-0080Me Me H H 2 H H CF₃ Bu-t Cl 118-119 3-0081 Me Me H H 2 H H CF₃ Bu-s Cl110-112 3-0082 Me Me H H 2 H H Cl Bu-s CF₃ 110-111 3-0083 Me Me H H 2 HH CF₃ Bu-i Cl 96-98 3-0084 Me Me H H 2 H H Cl Bu-i CF₃ 140-141 3-0085 MeMe H H 2 H H CF₃ Bu Cl 89-90 3-0086 Me Me H H 2 H H Cl Bu CF₃ 108-1103-0087 Me Me H H 2 H H CF₃ CH₂Ph Cl 132-133 3-0088 Me Me H H 2 H H ClCH₂Ph CF₃ 118-120 3-0089 Me Me H H 2 H H CF₃ Pen-c Cl 130-131 3-0090 MeMe H H 2 H H Cl Pen-c CF₃ 147-148 3-0091 Me Me H H 2 H H CF₃ Hex-c Cl151-152 3-0092 Me Me H H 2 H H CF₃ CH₂Pr-c Cl 93-95 3-0093 Me Me H H 2 HH Cl CH₂Pr-c CF₃ 129-130 3-0094 Me Me H H 2 H H CF₃ 1-cyclopropylethylCl 87-89 3-0095 Me Me H H 2 H H Cl 1-cyclopropylethyl CF₃ 121-123 3-0096Me Me H H 2 H H CF₃ CH₂(2-Methylcyclopropyl) Cl 102-103 3-0097 Me Me H H2 H H Cl CH₂(2-Methylcyclopropyl) CF₃ 118-119 3-0098 Me Me H H 2 H H CF₃CH₂Bu-c Cl 94-96 3-0099 Me Me H H 2 H H Cl CH₂Bu-c CF₃ 141-142 3-0100 MeMe H H 2 H H CF₃ CH₂Pen-c Cl 127-129 3-0101 Me Me H H 2 H H Cl CH₂Pen-cCF₃ 146-149 3-0102 Me Me H H 2 H H CF₃ CH₂Hex-c Cl 152-154 3-0103 Me MeH H 2 H H Cl CH₂Hex-c CF₃ 115-117 3-0104 Me Me H H 2 H H CF₃ CH₂CH═CH₂Cl 78-80 3-0105 Me Me H H 2 H H Cl CH₂CH═CH₂ CF₃ 105-106 3-0106 Me Me HH 2 H H CF₃ CH₂C≡CH Cl 73-74 3-0107 Me Me H H 2 H H Cl CH₂C≡CH CF₃108-109 3-0108 Me Me H H 2 H H CF₃ CHMeC≡CH Cl 95-96 3-0109 Me Me H H 2H H Cl CHMeC≡CH CF₃ 116-118 3-0110 Me Me H H 2 H H CF₃ CH₂C≡CMe Cl114-115 3-0111 Me Me H H 2 H H Cl CH₂C≡CMe CF₃ 115-116 3-0112 Me Me H H2 H H CF₃ CHF₂ OMe 72-74

TABLE 6 Melting point (° C.) or Comp. refractive No. R¹ R² R³ R⁴ n R⁵ R⁶R²⁹ R²⁸ R³⁰ index (n_(D) ²⁰) 3-0113 Me Me H H 2 H H OMe CHF₂ CF₃ 108-1093-0114 Me Me H H 2 H H CF₃ CH₂CHF₂ Cl  99-100 3-0115 Me Me H H 2 H H ClCH₂CHF₂ CF₃ 107-109 3-0116 Me Me H H 2 H H CF₃ CH₂CF₃ Cl 135-136 3-0117Me Me H H 2 H H Cl CH₂CF₃ CF₃ 112-115 3-0118 Me Me H H 2 H H CF₃ CH₂OMeCl 87-89 3-0119 Me Me H H 2 H H Cl CH₂OMe CF₃ 125-128 3-0120 Me Me H H 2H H CF₃ CH₂OEt Cl 97-98 3-0121 Me Me H H 2 H H Cl CH₂OEt CF₃ 128-1293-0122 Me Me H H 2 H H CF₃ CH₂CH₂OH Cl 79-81 3-0123 Me Me H H 2 H H ClCH₂CH₂OH CF₃ 93-94 3-0124 Me Me H H 2 H H CF₃ CH₂CH₂OMe Cl 102-1043-0125 Me Me H H 2 H H Cl CH₂CH₂OMe CF₃ 118-119 3-0126 Me Me H H 2 H HCF₃ CH₂CH₂OEt Cl 56-59 3-0127 Me Me H H 2 H H Cl CH₂CH₂OEt CF₃ 118-1193-0128 Me Me H H 2 H H CF₃ CH₂SMe Cl 103-105 3-0129 Me Me H H 2 H H ClCH₂SMe CF₃ 128-129 3-0130 Me Me H H 2 H H CF₃ CH₂SO₂Me Cl 157-159 3-0131Me Me H H 2 H H Cl CH₂SO₂Me CF₃ 165-166 3-0132 Me Me H H 2 H H CF₃CH₂CH₂SO₂Me Cl 155-157 3-0133 Me Me H H 2 H H Cl CH₂CH₂SO₂Me CF₃ 166-1683-0134 Me Me H H 2 H H CF₃ CH₂CN Cl 128-129 3-0135 Me Me H H 2 H H ClCH₂CN CF₃ 117-118 3-0136 Me Me H H 2 H H CF₃ CH₂C(═O)OEt Cl 127-1293-0137 Me Me H H 2 H H Cl CH₂C(═O)OEt CF₃ 143-145 3-0138 Me Me H H 2 H HCF₃ CH₂C(═O)NH₂ Cl 173-174 3-0139 Me Me H H 2 H H Cl CH₂C(═O)NH₂ CF₃182-183 3-0140 Me Me H H 2 H H CF₃ CH₂C(═O)N(Me)₂ Cl 142-143 3-0141 MeMe H H 2 H H Cl CH₂C(═O)N(Me)₂ CF₃ 181-182 3-0142 Me Me H H 2 H H CF₃CH₂C(═O)Me Cl 148-149 3-0143 Me Me H H 2 H H Cl CH₂C(═O)Me CF₃ 163-1643-0144 Me Me H H 2 H H CF₃ CH₂CH₂C(═O)Me Cl 89-91 3-0145 Me Me H H 2 H HMe Ph Me 140-141 3-0146 Me Me H H 2 H H Me Ph Cl 124-125 3-0147 Me Me HH 2 H H Et Ph Cl 112-113 3-0148 Me Me H H 2 H H Pr Ph Cl 122-123 3-0149Me Me H H 2 H H Pr-i Ph Cl 116-117 3-0150 Me Me H H 2 H H Bu-t Ph Cl100-102 3-0151 Me Me H H 2 H H CF₃ Ph H 111-112 Lr₃

TABLE 7 Melting point (° C.) Comp. or refractive No. R¹ R² R³ R⁴ n R⁵ R⁶R²⁹ R²⁸ R³⁰ index (n_(D) ²⁰) 3-0152 Me Me H H 2 H H CF₃ Ph Me 129-1323-0153 Me Me H H 2 H H CF₃ Ph CF₃ 112-113 3-0154 Me Me H H 2 H H CF₃ PhF 90-91 3-0155 Me Me H H 2 H H CF₃ Ph OMe 104-106 3-0156 Me Me H H 2 H HCF₃ Ph OEt 129-131 3-0157 Me Me H H 2 H H CF₃ Ph OPr-i 86-88 3-0158 MeMe H H 2 H H CF₃ Ph OPr 117-118 3-0159 Me Me H H 2 H H CF₃ Ph OBu-t105-108 3-0160 Me Me H H 2 H H CF₃ Ph OCHF₂ 90-92 3-0161 Me Me H H 2 H HCF₃ Ph SO₂Me 167-168 3-0162 Me Me H H 2 H H CF₃ Ph CN 113-115 3-0163 MeMe H H 2 H H CF₃ (2-Cl)Ph Cl 153-154 3-0164 Me Me H H 2 H H CF₃ (3-Cl)PhCl 106-107 3-0165 Me Me H H 2 H H CF₃ (4-Cl)Ph Cl 142-143 3-0166 Me Me HH 2 H H CF₃ (4-F)Ph Cl 135-138 3-0167 Me Me H H 2 H H CF₃ (4-OMe)Ph Cl136-138 3-0168 Me Me H H 2 H H CF₃ (4-Me)Ph Cl 129-130 3-0169 Me Me H H2 H H CF₃ (4-NO₂)Ph Cl 145-147 3-0170 Me Me H H 2 H H CF₃ (4-CN)Ph Cl91-93 3-0171 Me Me H H 2 H H CF₃ (4-C(═O)Me)Ph Cl 133-135 3-0172 Me Me HH 2 H H CF₃ (4-C(═O)OMe)Ph Cl 121-124 3-0173 Me Me H H 2 H H CF₃Pyrmidin-2-yl Cl 148-150 3-0174 Me Me H H 2 H H CF₃ 4,6-Dimethoxy- Cl117-118 pyrmidin-2-yl 3-0175 Me Me H H 2 H H CF₃ SO₂Me Cl 146-148 3-0176Me Me H H 2 H H CF₃ SO₂Ph Cl 145-148 3-0177 Me Me H H 2 H H CF₃ C(═O)MeCl 130-131 3-0178 Me Me H H 2 H H CF₃ C(═O)Ph Cl 114-117 3-0179 Me Me HH 2 H H CF₃ C(═O)OMe Cl 104-106 3-0180 Me Et H H 2 H H CF₃ Me Cl 108-1103-0181 Me Me H H 0 H H CHF₂ Me Cl 1.5183 3-0182 Me Me H H 0 H H Ph Me Cl76-77 3-0183 Me Me H H 0 H H CF₃ Bu-t OMe 1.4831 3-0184 Me Me H H 0 H HCF₃ CH₂C(═O)NH₂ Cl 179-180 3-0185 Me Me H H 0 H H Me Ph Cl 58-60 3-0186Me Me H H 0 H H CF₃ Me Cl 3-0187 Me Me H H 0 H H CF₃ Me OCHF₂ 3-0188 MeMe H H 2 H H CF₃ Me OCHF₂ 129-130 3-0189 Me Me H H 0 H H CF₃ Et OCHF₂3-0190 Me Me H H 2 H H CF₃ Et OCHF₂  98-100

TABLE 8

Melting point (° C.) or refractive Comp. index No. R¹ R² R³ R⁴ n R⁵ R⁶Z³ R³¹ R³² (n_(D) ²⁰) 4-0001 Me Me H H 2 H H O CF₃ Me 135-136 4-0002 MeMe H H 2 H H S Me Cl 113-114 4-0003 Me Me H H 0 H H O CF₃ Me 4-0004 MeMe H H 0 H H S Me Cl 4-0005 Me Me H H 2 H H O Me Me 178-179 4-0006 Me MeH H 2 H H O CF₃ OEt 89-91 4-0007 Me Me H H 2 H H O Ph Me 81-83 4-0008 MeMe H H 2 H H S Me OEt 109-111

TABLE 9

Melting point (° C.) or Comp. refractive No. R¹ R² R³ R⁴ n R⁵ R⁶ Z⁴ R³³R³⁴ index (n_(D) ²⁰) 5-0001 Me Me H H 2 H H NMe Cl Me 114-115 5-0002 MeMe H H 2 H H NMe Cl Et 107-108 5-0003 Me Me H H 2 H H NMe CF₃ H 142-1435-0004 Me Me H H 2 H H NCHF₂ —(CH₂)₄— 123-125 5-0005 Me Me H H 2 H H NPhOEt Me 1.5397 5-0006 Me Me H H 2 H H NPh OCHF₂ Me 1.5339 5-0007 Me Me HH 2 H H NPh CF₃ H 99-101 5-0008 Me Me H H 2 H H NPh OCH₂CH═CH₂ Me 87-905-0009 Me Me H H 1 H H NPh OCH₂CH═CH₂ Me 1.5702

TABLE 10

Melting point (° C.) or Comp. refractive No. R¹ R² R³ R⁴ n R⁵ R⁶ Z⁵ R³⁵R³⁶ index (n_(D) ²⁰) 6-0001 Me Me H H 2 H H NCHF₂ —(CH₂)₄— Unmesurable6-0002 Me Me H H 2 H H NPh H OEt 107-108 6-0003 Me Me H H 2 H H NPh HOCHF₂ 1.5383 6-0004 Me Me H H 2 H H O Me H 100-102 6-0005 Me Me H H 0 HH NCHF₂ —(CH₂)₄— 1.5264

TABLE 11

Melting point (° C.) or Comp. refractive No. R¹ R² R³ R⁴ n R⁵ R⁶ R³⁷ R³⁸R³⁹ R⁴⁰ index (n_(D) ²⁰) 7-0001 Me Me H H 2 H H H CF₃ H H — 77-80 7-0002Me Me H H 2 H H H CF₃ H H N-oxide 114-116 7-0003 Me Me H H 0 H H H CF₃ HH — 7-0004 Me Me H H 2 H H H H H H — 130-131 7-0005 Me Me H H 2 H H H HH H N-oxide 166-168 7-0006 Me Me H H 2 H H Cl Ph H H — 118-120 7-0007 MeMe H H 2 H H OMe Ph H H — 105-106 7-0008 Me Me H H 2 H H Cl Me H H —115-116 7-0009 Me Me H H 2 H H OMe Me H H — 134-135 7-0010 Me Me H H 2 HH Me Me H H N-oxide 198-199 7-0011 Me Me H H 2 H H Ph Ph H H — 161-1627-0012 Me Me H H 1 H H H H H H — 97-99 7-0013 Me Me H H 0 H H(2-Chloropyridin-3- H H H — 154-155 yl)methylthio

TABLE 12

Melting point (° C.) or Comp. refractive No. R¹ R² R³ R⁴ n R⁵ R⁶ R⁴¹ R⁴²R⁴³ index (n_(D) ²⁰) 8-0001 Me Me H H 2 H H H OMe CF₃ 175-176 8-0002 MeMe H H 0 H H H OMe CF₃ 8-0003 Me Me H H 2 H H H Cl Cl 119-120 8-0004 MeMe H H 2 H H H OEt CF₃ 94-95 8-0005 Me Me H H 2 H H H OMe OMe 186-1878-0006 Me Me H H 2 H H Me OMe CF₃ 143-144 8-0007 Me Me H H 2 H H OMe OMeCF₃ 144-145 8-0008 Me Me H H 2 H H SMe OMe CF₃ 160-162 8-0009 Me Me H H2 H H SO₂Me OMe CF₃ 144-146 8-0010 Me Me H H 2 H H NH₂ OMe CF₃ 208-2098-0011 Me Me H H 2 Pr-i H H H CF₃ 112-113 8-0012 Me Me H H 0 Pr-i H H HCF₃ 1.4986

TABLE 13

Melting point (° C.) or Comp. refractive No. R¹ R² R³ R⁴ n R⁵ R⁶ Y¹index (n_(D) ²⁰) 9-0001 Me Me H H 2 H H Pyridin-2-yl 116-118 9-0002 MeMe H H 2 H H Pyridin-2-yl 1-oxide 140-143 9-0003 Me Me H H 2 H HPyridin-4-yI 133-136 9-0004 Me Me H H 2 H H Pyridin-4-yl 1-oxide 110-1139-0005 Me Me H H 2 H H 1,2,4-Oxadiazol-3-yl Unmesurable 9-0006 Me Me H H2 H H 3-Phenyl-1,2,4-oxadiazol-5-yl 153-154 9-0007 Me Me H H 2 H H3-Benzyl-1,2,4-oxadiazol-5-yl 108-109 9-0008 Me Me H H 2 H H2-Chlorothiazol-4-yl 110-112 9-0009 Me Me H H 2 H H1,4-Dimethylimidazol-5-yl 163-164 9-0010 Me Me H H 1 H H Pyridin-2-yl81-82 9-0011 Me Me H H 1 H H Pyridin-4-yl 94-96 9-0012 Me Me H H 1 H H1,4-Dimethylimidazol-5-yl 138-140 9-0013 Me Me H H 0 H H1,4-Dimethylimidazol-5-yl 1.5427

TABLE 14

Melting point (° C.) or Comp. refractive No. R¹ R² R³ R⁴ n R⁵ R⁶ Y¹index (n_(D) ²⁰) 10-0001 Me Me H H 2 H H Benzimidazol-2-yl 171-17410-0002 Me Me H H 2 H H Benzothiophen-2-yl 181-183 10-0003 Me Me H H 2 HH 3-Chlorobenzothiophen-2-yl 109-112 10-0004 Me Me H H 2 H HBenzotriazol-1-yl 206-207 10-0005 Me Me H H 2 H H 1-Methylindazol-4-yl128-130 10-0006 Me Me H H 2 H H Benzothiazol-2-yl 142-143 10-0007 Me MeH H 2 H H Benzothiophen-3-yl 188-191 10-0008 Me Me H H 2 H H5-Chlorobenzothiophen-3-yl 129-130 10-0009 Me Me H H 2 H HBenzoxazol-2-yl 127-129 10-0010 Me Me H H 2 H H3-Methylbenzothiophen-2-yl 161-163 10-0011 Me Me H H 2 H H3-Bromobenzothiophen-2-yl 118-119 10-0012 Me Me H H 2 H HBenzofuran-2-yl 123-124 10-0013 Me Me H H 2 H H 2-Methylbenzofuran-7-yl135-137 10-0014 Me Me H H 2 H H 3-Bromobenzofuran-2-yl 107-108 10-0015Me Me H H 2 H H Benzothiophen-7-yl 95-97 10-0016 Me Me H H 2 H H1-Methylindazol-7-yl 89-90 10-0017 Me Me H H 2 H H3-Methylbenzofuran-2-yl 111-112 10-0018 Me Me H H 2 H H3-Chloro-1-methylindol-2-yl 162-165

In using the composition of the present invention as a herbicide, thepresent composition may be used in a mixture by itself without addingother compounds, but it can also be used in the form of a wettablepowder, granules, fine granules, a powder, an emulsifiable concentrate,a solution, a suspension, a flowable, etc. by mixing with a carrier, asurfactant, a dispersant, an adjuvant, etc. all generally usable informulation.

As the carrier usable in formulation, there can be mentioned, forexample, solid carriers such as talc, bentonite, clay, kaolin,diatomaceous earth, white carbon, vermiculite, calcium carbonate, slakedlime, siliceous sand, ammonium sulfate, urea and the like; and liquidcarriers such as isopropyl alcohol, xylene, cyclohexane,methylnaphthalene and the like.

As the surfactant and the dispersant, there can be mentioned, forexample, metal salts of alkylbenzenesulfonic acids, metal salts of analkylnaphthalenesulfonic acid-formalin condensate, salts of alcoholsulfates, alkylarylsulfonic acid salts, ligninsulfonic acid salts,polyoxyethylene glycol ethers, polyoxyethylene alkyl aryl ethers,monoalkylates of polyoxyethylene sorbitan and the like. As the adjuvant,there can be mentioned, for example, carboxymethyl cellulose,polyethylene glycol and gum arabic.

Also, the composition of the present invention may be prepared byformulating respective active ingredients in the above-mentioned mannerand then mixing the respective ingredients. The composition of thepresent invention thus formulated may be applied to plants as it is ormay be applied after diluting with water or the like. The composition ofthe present invention may be mixed with other herbicides to enhance itsherbicidal effect, or may be used further in combination with aninsecticide, a fungicide, a plant growth-regulating agent, a fertilizer,a soil-improving agent or the like.

The composition of the present invention contains an isoxazolinederivative of the formula (I) or its salt and at least one compoundselected from Group A preferably in a total amount of from 0.5 to 90 wt%, more preferably from 1 to 80 wt %.

Also, an isoxazoline derivative of the formula (I) or its salt may bemixed with two or more compounds selected from Group A, and itsapplication amount is preferably from 0.5 to 90 wt %, more preferablyfrom 1 to 80 wt %, in a total amount of the two ingredients.

The compound of the formula (I) used in the composition of the presentinvention can be prepared as illustrated in the following PreparationExamples, but should not be limited thereto.

PREPARATION EXAMPLE 1 Production of3-(5-chloro-1-phenyl-3-trifluoromethyl-1H-pyrazol-4-ylmethylthio)-5,5-dimethyl-2-isoxazoline(Present Compound No. 3-0001)

2.1 g of sodium hydrosulfide hydrate (purity: 70%, 26.2 mmoles) wasadded to a solution of 2.3 g (13.1 mmoles) of3-methylsulfonyl-5,5-dimethyl-2-isoxazoline dissolved in 20 ml ofN,N-dimethylformamide. The mixture was stirred for 2 hours. Thereto wereadded 1.8 g (13.1 mmoles) of anhydrous potassium carbonate, 2.0 g (13.1mmoles) of Rongalit and 3.6 g (10.5 mmoles) of4-bromomethyl-5-chloro-1-phenyl-3-trifluoromethyl-1H-pyrazole. Theresulting mixture was stirred at room temperature for 15 hours to giverise to a reaction. After the completion of the reaction, the reactionmixture was poured into water, followed by extraction with ethylacetate. The resulting organic layer was washed with an aqueous sodiumchloride solution and then dried over anhydrous magnesium sulfate. Theresulting solution was subjected to vacuum distillation to remove thesolvent contained therein. The residue was purified by silica gel columnchromatography (developing solvent: hexane-ethyl acetate mixed solvent)to obtain 2.7 g (yield: 65.5%) of3-(5-chloro-1-phenyl-3-trifluoromethyl-1H-pyrazol-4-ylmethylthio)-5,5-dimethyl-2-isoxazolineas white crystals (melting point: 89 to 90° C.).

¹H-NMR [CDCl₃/TMS, δ (ppm)]:

7.55-7.50 (5H,m), 4.33 (2H,s), 2.83 (2H,s), 1.45 (6H,s)

PREPARATION EXAMPLE 2 Production of3-(5-chloro-1-phenyl-3-trifluoromethyl-1H-pyrazol-4-ylmethylsulfonyl)-5,5-dimethyl-2-isoxazoline(Present Compound No. 3-0002)

0.63 g of m-chloroperbenzoic acid (purity: 70%, 2.6 mmoles) was added,with ice-cooling, to a solution of 0.4 g (1.0 mmoles) of3-(5-chloro-1-phenyl-3-trifluoromethyl-1H-pyrazol-4-ylmethylthio)-5,5-dimethyl-2-isoxazolinedissolved in 15 ml of chloroform. The mixture was stirred at roomtemperature for 22 hours to give rise to a reaction. After thecompletion of the reaction, the reaction mixture was poured into water,followed by extraction with chloroform. The resulting organic layer waswashed with an aqueous sodium hydrogensulfite solution, an aqueoussodium hydrogencarbonate solution and an aqueous sodium chloridesolution in this order and then dried over anhydrous magnesium sulfate.The resulting solution was subjected to vacuum distillation to removethe solvent contained therein. The resulting crystals were washed withhexane to obtain 0.4 g (yield: 83.2%) of3-(5-chloro-1-phenyl-3-trifluoromethyl-1H-pyrazol-4-ylmethylsulfonyl)-5,5-dimethyl-2-isoxazolineas white crystals (melting point: 132 to 133° C.).

¹H-NMR [CDCl₃/TMS, δ (ppm)]:

7.60-7.51 (5H,m), 4.37 (2H,s), 3.14 (2H,s) 1.53 (6H,s)

PREPARATION EXAMPLE 3 Production of3-(5-chloro-1-methyl-3-phenyl-1H-pyrazol-4-ylmethylsulfinyl)-5,5-dimethyl-2-isoxazoline(Present Compound No. 3-0003)

0.87 g of m-chloroperbenzoic acid (purity: 70%, 3.54 mmoles) was added,with ice-cooling, to a solution of 0.85 g (2.53 mmoles) of3-(5-chloro-1-methyl-3-phenyl-1H-pyrazol-4-ylmethylthio)-5,5-dimethyl-2-isoxazolinedissolved in 30 ml of chloroform. The mixture was stirred at roomtemperature for 1 hour to give rise to a reaction. After the completionof the reaction, the reaction mixture was poured into water, followed byextraction with chloroform. The resulting organic layer was washed withan aqueous sodium hydrogensulfite solution, an aqueous sodiumhydrogencarbonate solution and an aqueous sodium chloride solution inthis order and then dried over anhydrous magnesium sulfate. Theresulting solution was subjected to vacuum distillation to remove thesolvent contained therein. The residue was purified by silica gel columnchromatography (developing solvent: hexane-ethyl acetate mixed solvent)to obtain 0.48 g (yield: 53.9%) of3-(5-chloro-1-methyl-3-phenyl-1H-pyrazol-4-ylmethylsulfinyl)-5,5-dimethyl-2-isoxazolineas a transparent viscous substance.

¹H-NMR [CDCl₃/TMS, δ (ppm)]:

7.63-7.60 (2H,m), 7.48-7.37 (3H,m), 4.29 (2H,q), 3.91 (3H,s), 3.12(1H,d), 2.79 (1H,d), 1.41 (3H,s), 1.35 (3H,s)

PREPARATION EXAMPLE 4 Production of5,5-dimethyl-3-(5-fluoro-1-phenyl-3-trifluoromethyl-1H-pyrazol-4-ylmethylthio)-2-isoxazoline(Present Compound No. 3-0021)

9.3 g of sodium hydrosulfide hydrate (purity: 70%, 116.3 mmoles) wasadded to a solution of 18.7 g (105.7 mmoles) of5,5-dimethyl-3-methylsulfonyl-2-isoxazoline (present compound No. 2-1)dissolved in 300 ml of N,N-dimethylformamide. The mixture was stirredfor 2 hours. The reaction system was ice-cooled. Thereto was added asolution of 30.3 g (93.8 mmoles) of4-bromomethyl-5-fluoro-1-phenyl-3-trifluoromethyl-1H-pyrazole dissolvedin 200 ml of N,N-dimethylformamide. The mixture was stirred at 0° C. for30 minutes to give rise to a reaction. After the completion of thereaction, the reaction mixture was poured into water, followed byextraction with ethyl acetate. The resulting organic layer was washedwith an aqueous sodium chloride solution and then dried over anhydrousmagnesium sulfate. The resulting solution was subjected to vacuumdistillation to remove the solvent contained therein. The residue waspurified by silica gel column chromatography (developing solvent:hexane-ethyl acetate mixed solvent) to obtain 13.11 g (yield: 37.4%) of5,5-dimethyl-3-(5-fluoro-1-phenyl-3-trifluoromethyl-1H-pyrazol-4-ylmethylthio)-2-isoxazolineas a yellow oily substance.

¹H-NMR [CDCl₃/TMS, δ (ppm)]:

7.65-7.39 (5H,m), 4.24 (2H,s), 2.81 (2H,s), 1.43 (6H,s)

PREPARATION EXAMPLE 5 Production of5,5-dimethyl-3-(5-ethylthio-1-phenyl-3-trifluoromethyl-1H-pyrazol-4-ylmethylthio)-2-isoxazoline(Present Compound No. 3-0022)

0.2 g (4.0 mmoles) of sodium hydroxide and 1 ml of water were added to asolution of 0.25 g (4.0 mmoles) of ethanethiol dissolved in 10 ml ofN,N-dimethylformamide. The mixture was stirred at room temperature for30 minutes. Thereto was added a solution of 0.5 g (1.4 mmoles) of5,5-dimethyl-3-(5-fluoro-1-phenyl-3-trifluoromethyl-1H-pyrazol-4-ylmethylthio)-2-isoxazolinedissolved in 5 ml of N,N-dimethylformamide. The resulting mixture wasstirred for 1 hour to give rise to a reaction. After the completion ofthe reaction, the reaction mixture was poured into water, followed byextraction with ethyl acetate. The resulting organic layer was washedwith an aqueous sodium chloride solution and then dried over anhydrousmagnesium sulfate. The resulting solution was subjected to vacuumdistillation to remove the solvent contained therein, to obtain 0.6 g(yield: 100%) of5,5-dimethyl-3-(5-ethylthio-1-phenyl-3-trifluoromethyl-1H-pyrazol-4-ylmethylthio)-2-isoxazoline.

¹H-NMR [CDCl₃/TMS, δ (ppm)]:

7.62-7.47 (5H,m), 4.44 (2H,s), 2.83 (2H,s), 2.50 (2H,q), 1.45 (6H,s),1.02 (3H,t)

PREPARATION EXAMPLE 6 Production of5,5-dimethyl-3-(5-ethylsulfonyl-1-phenyl-3-trifluoromethyl-1H-pyrazol-4-ylmethylsulfonyl)-2-isoxazoline(Present Compound No. 3-0004)

1.7 g of m-chloroperbenzoic acid (purity: 70%, 6.7 mmoles) was added,with ice-cooling, to a solution of 0.6 g (1.3 mmoles) of5,5-dimethyl-3-(5-ethylthio-1-phenyl-3-trifluoromethyl-1H-pyrazol-4-ylmethylthio)-2-isoxazolinedissolved in 10 ml of chloroform. The mixture was stirred at roomtemperature for 16 hours to give rise to a reaction. After thecompletion of the reaction, the reaction mixture was poured into water,followed by extraction with chloroform. The resulting organic layer waswashed with an aqueous sodium hydrogensulfite solution, an aqueoussodium hydrogencarbonate solution and an aqueous sodium chloridesolution in this order and then dried over anhydrous magnesium sulfate.The resulting solution was subjected to vacuum distillation to removethe solvent contained therein. The resulting crystals were washed withhexane to obtain 0.6 g (yield: 93.0%) of5,5-dimethyl-3-(5-ethylsulfonyl-1-phenyl-3-trifluoromethyl-1H-pyrazol-4-ylmethylsulfonyl)-2-isoxazolineas light yellow crystals (melting point: 158 to 160° C).

¹H-NMR [CDCl₃/TMS, δ (ppm)]:

7.58-7.54 (5H,m), 5.16 (2H,s), 3.18 (2H,s), 3.15 (2H,q), 1.55 (6H,s),1.24 (3H,t)

PREPARATION EXAMPLE 7 Production of5,5-dimethyl-3-(5-dimethylamino-1-phenyl-3-trifluoromethyl-1H-pyrazol-4-ylmethylthio)-2-isoxazoline(Present Compound 3-0023)

0.8 g (6.7 mmoles) of a 40% aqueous dimethylamine solution was added toa solution of 0.5 g (1.3 mmoles) of5,5-dimethyl-3-(5-fluoro-1-phenyl-3-trifluoromethyl-1H-pyrazol-4-ylmethylthio)-2-isoxazolinedissolved in 10 ml of N,N-dimethylformamide. The mixture was stirred at100° C. for 9 hours in a sealed tube. Thereto was added 3.0 g (26.6mmoles) of a 40% aqueous dimethylamine solution, and the resultingmixture was stirred for 9 hours to give rise to a reaction. After thecompletion of the reaction, the reaction mixture was poured into water,followed by extraction with ethyl acetate. The resulting organic layerwas washed with an aqueous sodium chloride solution and then dried overanhydrous sodium sulfate. The resulting solution was subjected to vacuumdistillation to remove the solvent contained therein. The residue waspurified by silica gel column chromatography (developing solvent:hexane-ethyl acetate mixed solvent) to obtain 0.4 g (yield: 80.6%) of5,5-dimethyl-3-(5-dimethylamino-1-phenyl-3-trifluoromethyl-1H-pyrazol-4-ylmethylthio)-2-isoxazoline.

¹H-NMR [CDCl₃/TMS, δ (ppm)]:

7.58-7.38 (5H,m), 4.35 (2H,s), 2.82 (2H,s), 2.77 (6H,s), 1.45 (6H,s)

PREPARATION EXAMPLE 8 Production of5,5-dimethyl-3-(5-dimethylamino-1-phenyl-3-trifluoromethyl-1H-pyrazol-4-ylmethylsulfonyl)-2-isoxazoline(Present Compound 3-0005)

0.7 g of m-chloroperbenzoic acid (purity: 70%, 2.7 mmoles) was added,with ice-cooling, to a solution of 0.4 g (1.1 mmoles) of5,5-dimethyl-3-(5-dimethylamino-1-phenyl-3-trifluoromethyl-1H-pyrazol-4-ylmethylthio)-2-isoxazolinedissolved in 10 ml of chloroform. The mixture was stirred at roomtemperature for 20 hours to give rise to a reaction. After thecompletion of the reaction, the reaction mixture was poured into water,followed by extraction with chloroform. The resulting organic layer waswashed with an aqueous sodium hydrogensulfite solution, an aqueoussodium hydrogencarbonate solution and an aqueous sodium chloridesolution in this order and then dried over anhydrous magnesium sulfate.The resulting solution was subjected to vacuum distillation to removethe solvent contained therein. The resulting crystals were washed withhexane to obtain 0.2 g (yield: 52.0%) of5,5-dimethyl-3-(5-dimethylamino-1-phenyl-3-trifluoromethyl-1H-pyrazol-4-ylmethylsulfonyl)-2-isoxazolineas a white powder (melting point: 150 to 151° C.).

¹H-NMR [CDCl₃/TMS, δ (ppm)]:

7.61-7.38 (5H,m), 4.75 (2H,s), 3.13 (2H,s), 2.76 (6H,s), 1.53 (6H,s)

PREPARATION EXAMPLE 9 Production of3-(1-tert-butyl-5-chloro-3-trifluoromethyl-1H-pyrazol-4-ylmethylthio)-5,5-dimethyl-2-isoxazoline(Present Compound No. 3-0006)

21.8 g of sodium hydrosulfide (purity: 70%, 272.5 mmoles) was added to asolution of 24.1 g (136.0 mmoles) of5,5-dimethyl-3-methylsulfonyl-2-isoxazoline dissolved in 200 ml ofN,N-dimethylformamide. The mixture was stirred for 1 hour. Thereto wereadded 18.8 g (136.2 mmoles) of anhydrous potassium carbonate and 21.0 g(136.2 mmoles) of Rongalit. The resulting mixture was stirred for 2hours. Thereto was added, with ice-cooling, 40 g (125 mmoles) of4-bromomethyl-1-tert-butyl-5-chloro-3-trifluoromethyl-1 H-pyrazole. Theresulting mixture was stirred at room temperature for 2 hours to giverise to a reaction. After the completion of the reaction, the reactionmixture was poured into water, followed by extraction with ethylacetate. The resulting organic layer was washed with water and anaqueous sodium chloride solution and then dried over anhydrous magnesiumsulfate. The resulting solution was subjected to vacuum distillation toremove the solvent contained therein. The residue was purified by silicagel column chromatography (developing solvent: hexane-ethyl acetatemixed solvent) to obtain 23.0 g (yield: 57.1%) of3-(1-tert-butyl-5-chloro-3-trifluoromethyl-1H-pyrazol-4-ylmethylthio)-5,5-dimethyl-2-isoxazolineas light pink crystals (melting point: 79.0 to 81.0° C.).

¹H-NMR [CDCl₃/TMS, δ (ppm)]:

4.24 (2H,s), 2.80 (2H,s), 1.71 (9H,s), 1.43 (6H,s)

PREPARATION EXAMPLE 10 Production of3-(5-chloro-3-trifluoromethyl-1H-pyrazol-4-ylmethylthio)-5,5-dimethyl-2-isoxazoline(Present Compound No. 3-0007)

19.8 g (53.4 mmoles) of3-(1-tert-butyl-5-chloro-3-trifluoromethyl-1H-pyrazol-4-ylmethylthio)-5,5-dimethyl-2-isoxazolinewas added to 170 ml of a 25% hydrogen bromide-acetic acid solution. Themixture was stirred at 40 to 50° C. for 2 hours to give rise to areaction. After the completion of the reaction was confirmed, thereaction mixture was poured into water, followed by extraction withethyl acetate. The resulting organic layer was washed with water and anaqueous sodium chloride solution and then dried over anhydrous magnesiumsulfate. The resulting solution was subjected to vacuum distillation toremove the solvent contained therein, to obtain 12.0 g (yield: 60.6%) of3-(5-chloro-3-trifluoromethyl-1H-pyrazol-4-ylmethylthio)-5,5-dimethyl-2-isoxazolineas light yellow crystals (melting point: 120.0 to 122.0° C.).

¹H-NMR [CDCl₃/TMS, δ (ppm)]:

4.26 (2H,s), 2.81 (2H,s), 1.44 (6H,s)

PREPARATION EXAMPLE 11 Production of3-(5-chloro-1-difluoromethyl-3-trifluoromethyl-1H-pyrazol-4-ylmethylthio)-5,5-dimethyl-2-isoxazoline(Present Compound No. 3-0008) and3-(3-chloro-1-difluoromethyl-5-trifluoromethyl-1H-pyrazol-4-ylmethylthio)-5,5-dimethyl-2-isoxazoline(Present Compound 3-0009)

3.1 g (22.5 mmoles) of anhydrous potassium carbonate was added to asolution of 2.3 g (7.3 mmoles) of3-(5-chloro-3-trifluoromethyl-1H-pyrazol-4-ylmethylthio)-5,5-dimethyl-2-isoxazolinedissolved in 50 ml of N,N-dimethylformamide. Thereinto was blownchlorodifluoromethane. The resulting mixture was stirred at 130 to 140°C. for 3 hours to give rise to a reaction. After confirmation of thecompletion of the reaction, the reaction mixture was pored into water,followed by extraction with ethyl acetate. The resulting organic layerwas washed with water and an aqueous sodium chloride solution and thendried over anhydrous magnesium sulfate. The resulting solution wassubjected to vacuum distillation to remove the solvent containedtherein. The residue was purified by silica gel column chromatography(developing solvent: hexane-ethyl acetate mixed solvent) to obtain 0.69g (yield: 25.8%) of3-(5-chloro-1-difluoromethyl-3-trifluoromethyl-1H-pyrazol-4-ylmethylthio)-5,5-dimethyl-2-isoxazolineas light yellow crystals (melting point: 41.0 to 42.0° C.) and 0.54 g(yield: 20.2%) of3-(3-chloro-1-difluoromethyl-5-trifluoromethyl-1H-pyrazol-4-ylmethylthio)-5,5-dimethyl-2-isoxazolineas a white powder (melting point: 89.0 to 90.0° C.).

3-(5-Chloro-1-difluoromethyl-3-trifluoromethyl-1H-pyrazol-4-ylmethylthio)-5,5-dimethyl-2-isoxazoline

¹H-NMR [CDCl₃/TMS, δ (ppm)]:

7.22 (1H,t), 4.25 (2H,s), 2.80 (2H,s), 1.44 (6H,s)3-(3-Chloro-1-difluoromethyl-5-trifluoromethyl-1H-pyrazol-4-ylmethylthio)-5,5-dimethyl-2-isoxazoline

¹H-NMR [CDCl₃/TMS, δ (ppm)]:

7.19 (1H,t), 4.28 (2H,s), 2.80 (2H,s), 1.44 (6H,s)

PREPARATION EXAMPLE 12 Production of3-(5-chloro-1-difluoromethyl-3-trifluoromethyl-1H-pyrazol-4-ylmethylsulfonyl)-5,5-dimethyl-2-isoxazoline(Present Compound No. 3-0010)

1.4 g of m-chloroperbenzoic acid (purity: 70%, 8.1 mmoles) was added,with ice-cooling, to a solution of 0.69 g (1.9 mmoles) of3-(5-chloro-1-difluoromethyl-3-trifluoromethyl-1H-pyrazol-4-ylmethylthio)-5,5-dimethyl-2-isoxazolinedissolved in 20 ml of chloroform. The mixture was stirred for 1 hour andthen at room temperature for 12 hours to give rise to a reaction. Afterconfirmation of the completion of the reaction, the reaction mixture waspoured into water, followed by extraction with chloroform. The resultingorganic layer was washed with an aqueous sodium hydrogensulfitesolution, an aqueous sodium hydrogencarbonate solution, water and anaqueous sodium chloride solution in this order and then dried overanhydrous magnesium sulfate. The resulting solution was subjected tovacuum distillation to remove the solvent contained therein. Theresulting solid was washed with n-hexane to obtain 0.4 g (yield: 53.3%)of3-(5-chloro-1-difluoromethyl-3-trifluoromethyl-1H-pyrazol-4-ylmethylsulfonyl)-5,5-dimethyl-2-isoxazolineas a white powder (melting point: 126.0 to 127.0° C.).

¹H-NMR [CDCl₃/TMS, δ (ppm)]:

7.26 (1H,t), 4.68 (2H,s), 3.11 (2H,s), 1.53 (6H,s)

PREPARATION EXAMPLE 13 Production of3-(3-chloro-1-difluoromethyl-5-trifluoromethyl-1H-pyrazol-4-ylmethylsulfonyl)-5,5-dimethyl-2-isoxazoline(Present Compound No. 3-0011)

1.1 g of m-chloroperbenzoic acid (purity: 70%, 6.4 mmoles) was added,with ice-cooling, to a solution of 0.54 g (1.5 mmoles) of3-(3-chloro-1-difluoromethyl-5-trifluoromethyl-1H-pyrazol-4-ylmethylthio)-5,5-dimethyl-2-isoxazolinedissolved in 20 ml of chloroform. The mixture was stirred for 1 hour andthen at room temperature for 12 hours to give rise to a reaction. Afterconfirmation of the completion of the reaction, the reaction mixture waspoured into water, followed by extraction with chloroform. The resultingorganic layer was washed with an aqueous sodium hydrogensulfitesolution, an aqueous sodium hydrogencarbonate solution, water and anaqueous sodium chloride solution in this order and then dried overanhydrous magnesium sulfate. The resulting solution was subjected tovacuum distillation to remove the solvent contained therein. Theresulting solid was washed with n-hexane to obtain 0.47 g (yield: 79.7%)of3-(3-chloro-1-difluoromethyl-5-trifluoromethyl-1H-pyrazol-4-ylmethylsulfonyl)-5,5-dimethyl-2-isoxazolineas a white powder (melting point: 136.0 to 137.0° C.).

¹H-NMR [CDCl₃/TMS, δ (ppm)]:

7.23 (1H,t), 4.71 (2H,s), 3.11 (2H,s), 1.53 (6H,s)

PREPARATION EXAMPLE 14 Production of5,5-dimethyl-3-(3-methoxy-1-methyl-5-trifluoromethyl-1H-pyrazol-4-ylmethylthio)-2-isoxazoline(Present Compound No. 3-0024)

3.1 g of sodium hydrosulfide hydrate (purity: 70%, 22.0 mmoles) wasadded to a solution of 3.3 g (17.3 mmoles) of5,5-dimethyl-3-ethylsulfonyl-2-isoxazoline dissolved in 10 ml ofN,N-dimethylformamide. The mixture was stirred for 2 hours. Thereto wereadded 3.1 g (22.0 mmoles) of anhydrous potassium carbonate, 2.7 g (17.5mmoles) of Rongalit and 4.0 g (17.5 mmoles) of4-chloromethyl-3-methoxy-1-methyl-5-trifluoromethyl-1H-pyrazole. Theresulting mixture was stirred at room temperature for 2 hours to giverise to a reaction. After the completion of the reaction, the reactionmixture was poured into water, followed by extraction with ethylacetate. The resulting organic layer was washed with an aqueous sodiumchloride solution and then dried over anhydrous magnesium sulfate. Theresulting solution was subjected to vacuum distillation to remove thesolvent contained therein. The residue was purified by silica gel columnchromatography (developing solvent: hexane-ethyl acetate mixed solvent)to obtain 2.8 g (yield: 52.0%) of5,5-dimethyl-3-(3-methoxy-1-methyl-5-trifluoromethyl-1H-pyrazol-4-ylmethylthio)-2-isoxazoline.

PREPARATION EXAMPLE 15 Production of5,5-dimethyl-3-(3-hydroxy-1-methyl-5-trifluoromethyl-1H-pyrazol-4-ylmethylthio)-2-isoxazoline(Present Compound No. 3-0025)

To 20 ml of a 25% hydrogen bromide acetic acid solution was added 3.3 g(10.6 mmoles) of5,5-dimethyl-3-(3-methoxy-1-methyl-5-trifluoromethyl-1H-pyrazol-4-ylmethylthio)-2-isoxazoline.The mixture was stirred at 50° C. for 3 hours to give rise to areaction. After the completion of the reaction, the reaction mixture wassubjected to vacuum distillation to remove the solvent containedtherein. The residue was poured into water. The resulting crystals werecollected by filtration, washed with water and dried to obtain 3.1 g(yield: 96.0%) of intended5,5-dimethyl-3-(3-hydroxy-1-methyl-5-trifluoromethyl-1H-pyrazol-4-ylmethylthio)-2-isoxazoline.

PREPARATION EXAMPLE 16 Production of5,5-dimethyl-3-(3-ethoxy-1-methyl-5-trifluoromethyl-1H-pyrazol-4-ylmethylthio)-2-isoxazoline(Present Compound No. 3-0026)

0.20 g (1.3 mmoles) of anhydrous potassium carbonate and 0.20 g (1.5mmoles) of ethyl iodide were added to a solution of 0.30 g (1.0 mmoles)of5,5-dimethyl-3-(3-hydroxy-1-methyl-5-trifluoromethyl-1H-pyrazol-4-ylmethylthio)-2-isoxazolinedissolved in 10 ml of N,N-dimethylformamide. The mixture was stirred at50° C. for 3 hours to give rise to a reaction. After the completion ofthe reaction, the reaction mixture was poured into water, followed byextraction with ethyl acetate. The resulting-organic layer was washedwith an aqueous sodium chloride solution and then dried over anhydrousmagnesium sulfate. The resulting solution was subjected to vacuumdistillation to remove the solvent contained therein, to obtain 0.30 g(yield: 92.0%) of intended5,5-dimethyl-3-(3-ethoxy-1-methyl-5-trifluoromethyl-1H-pyrazol-4-ylmethylthio)-2-isoxazoline.

PREPARATION EXAMPLE 17 Production of5,5-dimethyl-3-(3-ethoxy-1-methyl-5-trifluoromethyl-1H-pyrazol-4-ylmethylsulfonyl)-2-isoxazoline(Present Compound No. 3-0012)

0.68 g of m-chloroperbenzoic acid (purity: 70%, 2.76 mmoles) was added,with ice-cooling, to a solution of 0.30 g (0.92 mmoles) of5,5-dimethyl-3-(3-ethoxy-1-methyl-5-trifluoromethyl-1H-pyrazol-4-ylmethylthio)-2-isoxazolinedissolved in 10 ml of chloroform. The mixture was stirred at roomtemperature for 5 hours to give rise to a reaction. After the completionof the reaction, the reaction mixture was poured into water, followed byextraction with chloroform. The resulting organic layer was washed withan aqueous sodium hydrogensulfite solution, an aqueous sodiumhydrogencarbonate solution and an aqueous sodium chloride solution inthis order and then dried over anhydrous magnesium sulfate. Theresulting solution was subjected to vacuum distillation to remove thesolvent contained therein. The resulting crystals were washed withhexane to obtain 0.24 g (yield: 73.0%) of5,5-dimethyl-3-(3-ethoxy-1-methyl-5-trifluoromethyl-1H-pyrazol-4-ylmethylsulfonyl)-2-isoxazolineas white crystals (melting point: 124 to 125° C.).

¹H-NMR [CDCl₃/TMS, δ (ppm)]:

4.50 (2H,s), 4.27 (2H,q), 3.86 (3H,s), 3.04 (2H,s), 1.49 (6H,s), 1.39(3H,t)

PREPARATION EXAMPLE 18 Production of5,5-dimethyl-3-(5-fluoro-1-methyl-3-trifluoromethyl-1H-pyrazol-4-ylmethylthio)-2-isoxazoline(Present Compound No. 3-0027)

19.3 g of sodium hydrosulfide (purity: 70%, 344.6 mmoles) was added to asolution of 21.3 g (120.3 mmoles) of5,5-dimethyl-3-methylsulfonyl-2-isoxazoline dissolved in 200 ml ofN,N-dimethylformamide. The mixture was stirred for 1 hour. Thereto wereadded 16.7 g (121.0 mmoles) of anhydrous potassium carbonate and 18.6 g(120.7 mmoles) of Rongalit. The resulting mixture was stirred for 2hours. Thereto was added, with ice-cooling, 31.4 g (120.3 mmoles) of4-bromomethyl-5-fluoro-1-methyl-3-trifluoromethyl-1H-pyrazole. Theresulting mixture was stirred at room temperature for 2 hours to giverise to a reaction. After confirmation of the completion of thereaction, the reaction mixture was poured into water, followed byextraction with ethyl acetate. The resulting organic layer was washedwith water and an aqueous sodium chloride solution and then dried overanhydrous magnesium sulfate. The resulting solution was subjected tovacuum distillation to remove the solvent contained therein, to obtain29.0 g (yield: 90.3%) of5,5-dimethyl-3-(5-fluoro-1-methyl-3-trifluoromethyl-1H-pyrazol-4-ylmethylthio)-2-isoxazolineas a yellow oily substance.

¹H-NMR [CDCl₃/TMS, δ (ppm)]:

4.24 (2H,s), 3.90 (3H,s), 2.78 (2H,s), 1.42 (6H,s)

PREPARATION EXAMPLE 19 Production of5,5-dimethyl-3-(5-methoxy-1-methyl-3-trifluoromethyl-1H-pyrazol-4-ylmethylthio)-2-isoxazoline(Present Compound No. 3-0028)

0.77 g (4.0 mmoles) of sodium methoxide (a 28% methanol solution) wasadded to a solution of 0.5 g (1.6 mmoles) of5,5-dimethyl-3-(5-fluoro-1-methyl-3-trifluoromethyl-1H-pyrazol-4-ylmethylthio)-2-isoxazolinedissolved in 20 ml of methanol. The mixture was stirred for 4 hoursunder refluxing, to give rise to a reaction. After confirmation of thecompletion of the reaction, the reaction mixture was poured into water,followed by extraction with ethyl acetate. The resulting organic layerwas washed with water and an aqueous sodium chloride solution and thendried over anhydrous magnesium sulfate. The resulting solution wassubjected to vacuum distillation to remove the solvent containedtherein, to obtain 0.5 g (yield: 96.7%) of5,5-dimethyl-3-(5-methoxy-1-methyl-3-trifluoromethyl-1H-pyrazol-4-ylmethylthio)-2-isoxazolineas a yellow oily substance.

¹H-NMR [CDCl₃/TMS, δ (ppm)]:

4.26 (2H,s), 4.07 (3H,s), 3.72 (3H,s), 2.80 (2H,s), 1.43 (6H,s)

PREPARATION EXAMPLE 20 Production of5,5-dimethyl-3-(5-methoxy-1-methyl-3-trifluoromethyl-1H-pyrazol-4-ylmethylsulfonyl)-2-isoxazoline(Present Compound No. 3-0013)

1.3 g of m-chloroperbenzoic acid (purity: 70%, 7.5 mmoles) was added,with ice-cooling, to a solution of 0.5 g (1.5 mmoles) of5,5-dimethyl-3-(5-methoxy-1-methyl-3-trifluoromethyl-1H-pyrazol-4-ylmethylthio)-2-isoxazolinedissolved in 20 ml of chloroform. The mixture was stirred for 1 hour andthen at room temperature for 12 hours to give rise to a reaction. Afterconfirmation of the completion of the reaction, the reaction mixture waspoured into water, followed by extraction with chloroform. The resultingorganic layer was washed with an aqueous sodium hydrogensulfitesolution, an aqueous sodium hydrogencarbonate solution, water and anaqueous sodium chloride solution in this order and then dried overanhydrous magnesium sulfate. The resulting solution was subjected tovacuum distillation to remove the solvent contained therein. Theresulting solid was washed with n-hexane to obtain 0.31 g (yield: 58.2%)of5,5-dimethyl-3-(5-methoxy-1-methyl-3-trifluoromethyl-1H-pyrazol-4-ylmethylsulfonyl)-2-isoxazolineas a white powder (melting point: 113.0 to 114.0° C.).

¹H-NMR [CDCl₃/TMS, δ (ppm)]:

4.60 (2H,s), 4.11 (3H,s), 3.79 (3H,s), 3.10 (2H,s), 1.51(6H,s)

PREPARATION EXAMPLE 21 Production of3-(5-(2-chlorophenoxy)-1-methyl-3-trifluoromethyl-1H-pyrazol-4-ylmethylthio)-5,5-dimethyl-2-isoxazoline(Present Compound No. 3-0029)

0.2 g (8.3 mmoles) of sodium hydride (purity: 60%) was added, withice-cooling, to a solution of 0.44 g (3.4 mmoles) of 2-chlorophenoldissolved in 30 ml of N,N-dimethylformamide. The mixture was stirred for1 hour. Thereto was added 0.7 g (2.2 mmoles) of5,5-dimethyl-3-(5-fluoro-1-methyl-3-trifluoromethyl-1H-pyrazol-4-ylmethylthio)-2-isoxazoline.The resulting mixture was stirred at 120 to 130° C. for 5 hours to giverise to a reaction. After confirmation of the completion of thereaction, the reaction mixture was poured into water, followed byextraction with ethyl acetate. The resulting organic layer was washedwith water and an aqueous sodium chloride solution and then dried overanhydrous magnesium sulfate. The resulting solution was subjected tovacuum distillation to remove the solvent contained therein. The residuewas purified by silica gel column chromatography (developing solvent:hexane-ethyl acetate mixed solvent) to obtain 0.63 g (yield: 66.7%) of3-(5-(2-chlorophenoxy)-1-methyl-3-trifluoromethyl-1H-pyrazol-4-ylmethylthio)-5,5-dimethyl-2-isoxazolineas a yellow oily substance.

PREPARATION EXAMPLE 22 Production of3-(5-(2-chlorophenoxy)-1-methyl-3-trifluoromethyl-1H-pyrazol-4-ylmethylsulfonyl)-5,5-dimethyl-2-isoxazoline(Present Compound No. 3-0014)

1.0 g of m-chloroperbenzoic acid (purity: 70%, 5.8 mmoles) was added,with ice-cooling, to a solution of 0.63 g (1.5 mmoles) of3-(5-(2-chlorophenoxy)-1-methyl-3-trifluoromethyl-1H-pyrazol-4-ylmethylthio)-5,5-dimethyl-2-isoxazolinedissolved in 20 ml of chloroform. The mixture was stirred for 1 hour andthen at room temperature for 12 hours to give rise to a reaction. Afterconfirmation of the completion of the reaction, the reaction mixture waspoured into water, followed by extraction with chloroform. The resultingorganic layer was washed with an aqueous sodium hydrogensulfitesolution, an aqueous sodium hydrogencarbonate solution, water and anaqueous sodium chloride solution in this order and then dried overanhydrous magnesium sulfate. The resulting solution was subjected tovacuum distillation to remove the solvent contained therein. Theresulting solid was washed with n-hexane to obtain 0.31 g (yield: 45.7%)of3-(5-(2-chlorophenoxy)-1-methyl-3-trifluoromethyl-1H-pyrazol-4-ylmethylsulfonyl)-5,5-dimethyl-2-isoxazolineas a white powder (melting point: 67.0 to 70.0° C.).

¹H-NMR [CDCl₃/TMS, δ (ppm)]:

7.50-6.91 (4H,m), 4.45 (2H,s), 3.71 (3H,s), 3.03 (2H,s), 1.47 (6H,s)

PREPARATION EXAMPLE 23 Production of3-(5-cyclopentyloxy-1-methyl-3-trifluoromethyl-1H-pyrazol-4-ylmethylthio)-5,5-dimethyl-2-isoxazoline(Present Compound No. 3-0030)

To a solution of 0.43 g (1.6 mmoles) of triphenylphosphine dissolved in10 ml of benzene were added 0.14 g (1.6 mmoles) of cyclopentanol, 0.5 g(1.6 mmoles) of5,5-dimethyl-3-(5-hydroxy-1-methyl-3-trifluoromethyl-1H-pyrazol-4-ylmethylthio)-2-isoxazolineand 0.7 g (1.6 mmoles) of diethyl azodicarboxylate (a 40% toluenesolution). The mixture was stirred at room temperature for 12 hours togive rise to a reaction. After confirmation of the completion of thereaction, the reaction mixture was poured into water, followed byextraction with ethyl acetate. The resulting organic layer was washedwith water and an aqueous sodium chloride solution and then dried overanhydrous magnesium sulfate. The resulting organic layer was subjectedto vacuum distillation to remove the solvent contained therein. Theresidue was purified by silica gel column chromatography (developingsolvent: hexane-ethyl acetate mixed solvent) to obtain 0.52 g (yield:85.2%) of3-(5-cyclopentyloxy-1-methyl-3-trifluoromethyl-1H-pyrazol-4-ylmethylthio)-5,5-dimethyl-2-isoxazolineas a colorless transparent oily substance.

PREPARATION EXAMPLE 24 Production of3-(5-cyclopentyloxy-1-methyl-3-trifluoromethyl-1H-pyrazol-4-ylmethylsulfonyl)-5,5-dimethyl-2-isoxazoline(Present Compound No. 3-0015)

0.85 g of m-chloroperbenzoic acid (purity: 70%, 4.9 mmoles) was added,with ice-cooling, to a solution of 0.52 g (1.4 mmoles) of3-(5-(cyclopentyloxy-1-methyl-3-trifluoromethyl-1H-pyrazol-4-ylmethylthio)-5,5-dimethyl-2-isoxazolinedissolved in 20 ml of chloroform. The mixture was stirred for 1 hour andthen at room temperature for 12 hours to give rise to a reaction. Afterconfirmation of the completion of the reaction, the reaction mixture waspoured into water, followed by extraction with chloroform. The resultingorganic layer was washed with an aqueous sodium hydrogensulfitesolution, an aqueous sodium hydrogencarbonate solution, water and anaqueous sodium chloride solution in this order and then dried overanhydrous magnesium sulfate. The resulting solution was subjected tovacuum distillation to remove the solvent contained therein. Theresulting solid was washed with n-hexane to obtain 0.2 g (yield: 35.5%)of3-(5-cyclopentyloxy-1-methyl-3-trifluoromethyl-1H-pyrazol-4-ylmethylsulfonyl)-5,5-dimethyl-2-isoxazolineas a white powder (melting point: 113.0 to 114.0° C.).

¹H-NMR [CDCl₃/TMS, δ (ppm)]:

5.03 (1H,br), 4.60 (2H,s), 3.73 (3H,s), 3.05 (2H,s), 1.88-1.70 (8H,m),1.50 (6H,s)

PREPARATION EXAMPLE 25 Production of3-(5-cyano-1-methyl-3-trifluoromethyl-1H-pyrazol-4-ylmethylthio)-5,5-dimethyl-2-isoxazoline(Present Compound No. 3-0031)

0.2 g (4.0 mmoles) of sodium cyanide was added to a solution of 0.5 g(1.6 mmoles) of5,5-dimethyl-3-(5-fluoro-1-methyl-3-trifluoromethyl-1H-pyrazol-4-ylmethylthio)-2-isoxazolinedissolved in 30 ml of N,N-dimethylformamide. The mixture was stirred at40° C. for 1 hour to give rise to a reaction. After confirmation of thecompletion of the reaction, the reaction mixture was poured into water,followed by extraction with ethyl acetate. The resulting organic layerwas washed with water and an aqueous sodium chloride solution and thendried over anhydrous magnesium sulfate. The resulting solution wassubjected to vacuum distillation to remove the solvent containedtherein, to obtain 0.9 g of crude3-(5-cyano-1-methyl-3-trifluoromethyl-1H-pyrazol-4-ylmethylthio)-5,5-dimethyl-2-isoxazolineas a yellow oily substance.

¹H-NMR [CDCl₃/TMS, δ (ppm)]:

4.30 (2H,s), 4.08 (3H,s), 2.81 (2H,s), 1.43 (6H,s)

PREPARATION EXAMPLE 26 Production of3-(5-cyano-1-methyl-3-trifluoromethyl-1H-pyrazol-4-ylmethylsulfonyl)-5,5-dimethyl-2-isoxazoline(Present Compound No. 3-0016)

2.1 g of m-chloroperbenzoic acid (purity: 70%, 12.2 mmoles) was added,with ice-cooling, to a solution of 0.9 g of3-(5-cyano-1-methyl-3-trifluoromethyl-1H-pyrazol-4-ylmethylthio)-5,5-dimethyl-2-isoxazoline(crude compound) dissolved in 50 ml of chloroform. The mixture wasstirred for 1 hour and then at room temperature for 12 hours to giverise to a reaction. After confirmation of the completion of thereaction, the reaction mixture was poured into water, followed byextraction with chloroform. The resulting organic layer was washed withan aqueous sodium hydrogensulfite solution, an aqueous sodiumhydrogencarbonate solution, water and an aqueous sodium chloridesolution in this order and then dried over anhydrous magnesium sulfate.The resulting solution was subjected to vacuum distillation to removethe solvent contained therein. The resulting solid was washed withn-hexane to obtain 0.43 g (yield: 76.4%) of3-(5-cyano-1-methyl-3-trifluoromethyl-1H-pyrazol-4-ylmethylsulfonyl)-5,5-dimethyl-2-isoxazolineas a white powder (melting point: 105.0 to 108.0° C.).

¹H-NMR [CDCl₃/TMS, δ (ppm)]:

4.73 (2H,s), 4.16 (3H,s), 3.14 (2H,s), 1.53 (6H,s)

PREPARATION EXAMPLE 27 Production of3-(3,5-dichloro-1-ethyl-1H-pyrazol-4-ylmethylthio)-5,5-dimethyl-2-isoxazoline(Present Compound No. 3-0032)

0.6 g of sodium hydrosulfide (purity: 70%, 10.7 mmoles) was added to asolution of 0.7 g (3.7 mmoles) of5,5-dimethyl-3-ethylsulfonyl-2-isoxazoline dissolved in 30 ml ofN,N-dimethylformamide. The mixture was stirred for 1 hour. Thereto wereadded 0.51 g (3.7 mmoles) of anhydrous potassium carbonate and 0.56 g(3.6 mmoles) of Rongalit. The resulting mixture was stirred for 2 hours.Thereto was added, with ice-cooling, 0.9 g (3.5 mmoles) of4-bromomethyl-3,5-dichloro-1-ethyl-1H-pyrazole. The resulting mixturewas stirred at room temperature for 2 hours to give rise to a reaction.After confirmation of the completion of the reaction, the reactionmixture was poured into water, followed by extraction with ethylacetate. The resulting organic layer was washed with water and anaqueous sodium chloride solution and then dried over anhydrous magnesiumsulfate. The resulting solution was subjected to vacuum distillation toremove the solvent contained therein. The residue was purified by silicagel column chromatography (developing solvent: hexane-ethyl acetatemixed solvent) to obtain 0.8 g (yield: 70.8%) of3-(3,5-dichloro-1-ethyl-1H-pyrazol-4-ylmethylthio)-5,5-dimethyl-2-isoxazolineas a colorless transparent oily substance.

¹H-NMR [CDCl₃/TMS, δ (ppm)]:

4.14 (2H,s), 4.14 (2H, q), 2.81 (2H,s), 1.43 (6H,s), 1.42 (3H,t)

PREPARATION EXAMPLE 28 Production of3-(3,5-dichloro-1-ethyl-1H-pyrazol-4-ylmethylsulfonyl)-5,5-dimethyl-2-isoxazoline(Present Compound No. 3-0017)

2.0 g of m-chloroperbenzoic acid (purity: 70%, 11.6 mmoles) was added,with ice-cooling, to a solution of 0.8 g (2.6 mmoles) of3-(3,5-dichloro-1-ethyl-1H-pyrazol-4-ylmethylthio)-5,5-dimethyl-2-isoxazolinedissolved in 20 ml of chloroform. The mixture was stirred for 1 hour andthen at room temperature for 12 hours to give rise to a reaction. Afterconfirmation of the completion of the reaction, the reaction mixture waspoured into water, followed by extraction with chloroform. The resultingorganic layer was washed with an aqueous sodium hydrogensulfitesolution, an aqueous sodium hydrogencarbonate solution, water and anaqueous sodium chloride solution in this order and then dried overanhydrous magnesium sulfate. The resulting solution was subjected tovacuum distillation to remove the solvent contained therein. Theresulting solid was washed with n-hexane to obtain 0.41 g (yield: 46.6%)of3-(3,5-dichloro-1-ethyl-1H-pyrazol-4-ylmethylsulfonyl)-5,5-dimethyl-2-isoxazolineas a white powder (melting point: 105.0 to 107.0° C.).

¹H-NMR [CDCl₃/TMS, δ (ppm)]:

4.48 (2H,s), 4.19 (2H,q), 3.05 (2H,s), 1.51 (6H,s), 1.45 (3H,t)

PREPARATION EXAMPLE 29 Production of3-(5-chloro-3-difluoromethyl-1-methyl-1H-pyrazol-4-ylmethylthio)-5,5-dimethyl-2-isoxazoline(Present Compound No. 3-0020)

1.2 g of sodium hydrosulfide hydrate (purity: 70%, 15.0 mmoles) wasadded to a solution of 1.9 g (10.0 mmoles) of5,5-dimethyl-3-ethylsulfonyl-2-isoxazoline dissolved in 30 ml ofN,N-dimethylformamide. The mixture was stirred for 2 hours. Thereto wereadded 2.1 g (15.0 mmoles) of anhydrous potassium carbonate, 2.3 g (15.0mmoles) of Rongalit and 2.6 g (10.0 mmoles) of4-bromomethyl-5-chloro-3-difluoromethyl-1-methyl-1H-pyrazole. Theresulting mixture was stirred at room temperature for 15 hours to giverise to a reaction. After the completion of the reaction, the reactionmixture was poured into water, followed by extraction with ethylacetate. The resulting organic layer was washed with an aqueous sodiumchloride solution and then dried over anhydrous magnesium sulfate. Theresulting solution was subjected to vacuum distillation to remove thesolvent contained therein. The residue was purified by silica gel columnchromatography (developing solvent: hexane-ethyl acetate mixed solvent)to obtain 2.1 g (yield: 68.0%) of3-(5-chloro-3-difluoromethyl-1-methyl-1H-pyrazol-4-ylmethylthio)-5,5-dimethyl-2-isoxazolineas a colorless viscous liquid (n_(D) ²⁰=1.5183).

¹H-NMR [CDCl₃/TMS, δ (ppm)]:

6.70 (1H,t, J=54.2 Hz), 4.24 (2H,s), 3.86 (3H,s), 2.80 (2H,s), 1.42(6H,s)

PREPARATION EXAMPLE 30 Production of3-(5-chloro-3-difluoromethyl-1-methyl-1H-pyrazol-4-ylmethylsulfonyl)-5,5-dimethyl-2-isoxazoline(Present Compound No. 3-0018)

3.6 g of m-chloroperbenzoic acid (purity: 70%, 14.5 mmoles) was added,with ice-cooling, to a solution of 1.8 g (5.8 mmoles) of3-(5-chloro-3-difluoromethyl-1-methyl-1H-pyrazol-4-ylmethylthio)-5,5-dimethyl-2-isoxazolinedissolved in 15 ml of chloroform. The mixture was stirred at roomtemperature for 22 hours to give rise to a reaction. After thecompletion of the reaction, the reaction mixture was poured into water,followed by extraction with chloroform. The resulting organic layer waswashed with an aqueous sodium hydrogensulfite solution, an aqueoussodium hydrogencarbonate solution and an aqueous sodium chloridesolution in this order and then dried over anhydrous magnesium sulfate.The resulting solution was subjected to vacuum distillation to removethe solvent contained therein. The resulting crystals were washed withhexane to obtain 1.7 g (yield: 85.9%) of3-(5-chloro-3-difluoromethyl-1-methyl-1H-pyrazol-4-ylmethylsulfonyl)-5,5-dimethyl-2-isoxazolineas white crystals (melting point: 78 to 79° C.).

¹H-NMR [CDCl₃/TMS, δ (ppm)]:

6.80 (1H,t, J=54.8 Hz), 4.60 (2H,s), 3.91 (3H,s), 3.08 (2H,s), 1.51(6H,s)

PREPARATION EXAMPLE 31 Production of5,5-dimethyl-3-(5-methyl-3-trifluoromethylisoxazol-4-ylmethylthio)-2-isoxazoline(Present Compound No. 4-0003)

0.4 g of sodium hydrosulfide hydrate (purity: 70%, 4.6 mmoles) was addedto a solution of 0.4 g (2.3 mmoles) of5,5-dimethyl-3-methylsulfonyl-2-isoxazoline dissolved in 10 ml ofN,N-dimethylformamide. The mixture was stirred for 2 hours. Thereto wereadded 0.3 g (2.3 mmoles) of potassium carbonate, 0.4 g (2.3 mmoles) ofRongalit and 0.5 g (1.8 mmoles) of4-bromomethyl-5-methyl-3-trifluoromethylisoxazole. The resulting mixturewas stirred at room temperature for 14 hours to give rise to a reaction.After the completion of the reaction, the reaction mixture was pouredinto water, followed by extraction with ethyl acetate. The resultingorganic layer was washed with an aqueous sodium chloride solution andthen dried over anhydrous magnesium sulfate. The resulting solution wassubjected to vacuum distillation to remove the solvent containedtherein. The residue was purified by silica gel column chromatography(developing solvent: hexane-ethyl acetate mixed solvent) to obtain 0.4 g(yield: 70.0%) of5,5-dimethyl-3-(5-methyl-3-trifluoromethylisoxazol-4-ylmethylthio)-2-isoxazoline.

¹H-NMR [CDCl₃/TMS, δ (ppm)]:

4.11 (2H,s), 2.77 (2H,s), 2.54 (3H,s), 1.42 (6H,s)

PREPARATION EXAMPLE 32 Production of5,5-dimethyl-3-(5-methyl-3-trifluoromethylisoxazol-4-ylmehtylsulfonyl)-2-isoxazoline(Present Compound No. 4-0001)

0.8 g of m-chloroperbenzoic acid (purity: 70%, 3.2 mmoles) was added,with ice-cooling, to a solution of 0.4 g (1.3 mmoles) of5,5-dimethyl-3-(5-methyl-3-trifluoromethylisoxazol-4-ylmehtylthio)-2-isoxazolinedissolved in 10 ml of chloroform. The mixture was stirred at roomtemperature for 4 hours to give rise to a reaction. After the completionof the reaction, the reaction mixture was poured into water, followed byextraction with chloroform. The resulting organic layer was washed withan aqueous sodium hydrogensulfite solution, an aqueous sodiumhydrogencarbonate solution and an aqueous sodium chloride solution inthis order and then dried over anhydrous magnesium sulfate. Theresulting solution was subjected to vacuum distillation to remove thesolvent contained therein. The resulting crystals were washed withhexane to obtain 0.4 g (yield: 95.0%) of5,5-dimethyl-3-(5-methyl-3-trifluoromethylisoxazol-4-ylmehtylsulfonyl)-2-isoxazolineas white crystals (melting point: 135 to 136° C.).

¹H-NMR [CDCl₃/TMS, δ (ppm)]:

4.54 (2H,s), 3.11 (2H,s), 2.61 (3H,s), 1.52 (6H,s)

PREPARATION EXAMPLE 33 Production of[(5-chloro-3-methyl-isothiazol-4-yl)-methylthio]-5,5-dimethyl-2-isoxazoline(Present Compound No. 4-0004)

0.82 g of sodium hydrosulfide (purity: 70%, 10.00 mmoles) was added atthe room temperature to a solution of 0.89 g (5.00 mmoles) of5,5-dimethyl-3-methylsulfonyl-2-isoxazoline dissolved in 10 ml ofN,N-dimethylformamide. The mixture was stirred for 2 hours. Thereto wereadded 0.70 g (5.00 mmoles) of anhydrous potassium carbonate, 0.78 g(5.00 mmoles) of Rongalit and 0.91 g (5.00 mmoles) of5-chloro-4-chloromethyl-3-methylisothiazole. The resulting mixture wasstirred at room temperature overnight to give rise to a reaction. Afterconfirmation of the completion of the reaction, the reaction mixture waspoured into water, followed by extraction with ethyl acetate. Theresulting organic layer was washed with water and an aqueous sodiumchloride solution and then dried over anhydrous magnesium sulfate. Theresulting solution was subjected to vacuum distillation to remove thesolvent contained therein. The residue was purified by silica gel columnchromatography to obtain 1.38 g (yield: quantitative) of[(5-chloro-3-methyl-isothiazol-4-yl)-methylthio]-5,5-dimethyl-2-isoxazoline.

PREPARATION EXAMPLE 34 Production of[(5-chloro-3-methyl-isothiazol-4-yl)-methylsulfonyl]-5,5-dimethyl-2-isoxazoline(Present Compound No. 4-0002)

2.96 g of m-chloroperbenzoic acid (purity: 70%, 12.00 mmoles) was added,with ice-cooling, to a solution of 1.38 g (5.00 mmoles) of[(5-chloro-3-methyl-isothiazol-4-yl)-methylthio]-5,5-dimethyl-2-isoxazolinedissolved in 20 ml of chloroform. The mixture was stirred for 1 hour andthen at room temperature for overnight to give rise to a reaction. Afterthe completion of the reaction, the reaction mixture was poured intowater, followed by extraction with chloroform. The resulting organiclayer was washed with an aqueous sodium hydrogensulfite solution, anaqueous sodium hydrogencarbonate solution and an aqueous sodium chloridesolution in this order and then dried over anhydrous magnesium sulfate.The resulting solution was subjected to vacuum distillation to removethe solvent contained therein. The reside was purified by silica gelcolumn chromatography to obtain 0.65 g (yield: 47.0%) of[(5-chloro-3-methyl-isothiazol-4-yl)-methylsulfonyl]-5,5-dimethyl-2-isoxazolineas a light yellow powder (melting point: 113 to 114° C.).

¹H-NMR [CDCl₃/TMS, δ (ppm)]:

8.89 (1H,s), 4.67 (2H,s), 3.05 (2H,s), 2.59 (3H,s), 1.51 (6H,s)

PREPARATION EXAMPLE 35 Production of5,5-dimethyl-3-[2,5-dimethyl-4-(1-methoxyiminoethyl)-thiophen-3-ylmethylthio]-2-isoxazoline(Present Compound No. 2-0002)

0.57 g (6.8 mmoles) of O-methylhydroxylamine hydrochloride and 0.56 g(6.8 mmoles) of sodium acetate were added to a solution of 1.0 g (3.4mmoles) of3-(4-acetyl-2,5-dimethylthiophen-3-ylmethylthio)-5,5-dimethyl-2-isoxazolinedissolved in 50 ml of ethanol. The mixture was stirred for 5 hours underrefluxing, to give rise to a reaction. After confirmation of thecompletion of the reaction, the reaction mixture was poured into water,followed by extraction with ethyl acetate. The resulting organic layerwas washed with water and an aqueous sodium chloride solution and thendried over anhydrous magnesium sulfate. The resulting solution wassubjected to vacuum distillation to remove the solvent containedtherein. The residue was purified by silica gel column chromatography(developing solvent: hexane-ethyl acetate mixed solvent) to obtain 0.4 g(36.4%) of5,5-dimethyl-3-[2,5-dimethyl-4-(1-methoxyiminoethyl)-thiophen-3-ylmethylthio]-2-isoxazolineas a yellow oily substance.

¹H-NMR [CDCl₃/TMS, δ (ppm)]:

4.21 (2H,s), 3.95 (3H,s), 2.76 (2H,s), 2.38 (3H,s), 2.34 (3H,s), 2.13(3H,s), 1.42 (6H,s)

PREPARATION EXAMPLE 36 Production of5,5-dimethyl-3-[2,5-dimethyl-4-(1-methoxyiminoethyl)-thiophen-3-ylmethylsulfonyl]-2-isoxazoline(Present Compound No. 2-0001)

0.61 g of m-chloroperbenzoic acid (purity: 70%, 3.5 mmoles) was added,with ice-cooling, to a solution of 0.4 g (1.2 mmoles) of5,5-dimethyl-3-[2,5-dimethyl-4-(1-methoxyiminoethyl)-thiophen-3-ylmethylthio]-2-isoxazolinedissolved in 30 ml of chloroform. The mixture was stirred for 1 hour andthen at room temperature for 12 hours to give rise to a reaction. Afterconfirmation of the completion of the reaction, the reaction mixture waspoured into water, followed by extraction with chloroform. The resultingorganic layer was washed with an aqueous sodium hydrogensulfitesolution, an aqueous sodium hydrogencarbonate solution, water and anaqueous sodium chloride solution in this order and then dried overanhydrous magnesium sulfate. The resulting solution was subjected tovacuum distillation to remove the solvent contained therein. The residuewas purified by silica gel column chromatography (developing solvent:hexane-ethyl acetate mixed solvent) to obtain 0.35 g (80%) of5,5-dimethyl-3-[2,5-dimethyl-4-(1-methoxyiminoethyl)-thiophen-3-ylmethylsulfonyl]-2-isoxazolineas white crystals (melting point: 95.0 to 96.0° C.).

¹H-NMR [CDCl₃/TMS, δ (ppm)]:

4.79 (2H,s), 3.95 (3H,s), 2.93 (2H,s), 2.42 (3H,s), 2.37 (3H,s), 2.17(3H,s), 1.47 (6H,s)

PREPARATION EXAMPLE 37 Production of5,5-dimethyl-3-(4-trifluoromethyl-pyridin-3-ylmethylthio)-2-isoxazoline(Present Compound No. 7-0003)

0.26 g of sodium hydrosulfide (purity: 70%, 4.6 mmoles) was added to asolution of 0.3 g (1.6 mmoles) of5,5-dimethyl-3-ethylsulfonyl-2-isoxazoline dissolved in 20 ml ofN,N-dimethylformamide. The mixture was stirred for 1 hour. Thereto wereadded 0.22 g (1.6 mmoles) of anhydrous potassium carbonate and 0.25 g(1.6 mmoles) of Rongalit. The resulting mixture was stirred for 2 hours.Thereto was added, with ice-cooling, 0.3 g (1.3 mmoles) of3-bromomethyl-4-trifluoromethyl-pyridine. The resulting mixture wasstirred at room temperature for 2 hours to give rise to a reaction.After confirmation of the completion of the reaction, the reactionmixture was poured into water, followed by extraction with ethylacetate. The resulting organic layer was washed with water and anaqueous sodium chloride solution and then dried over anhydrous magnesiumsulfate. The resulting solution was subjected to vacuum distillation toremove the solvent contained therein. The residue was purified by silicagel column chromatography (developing solvent: hexane-ethyl acetatemixed solvent) to obtain 0.45 g (yield: 98.9%) of5,5-dimethyl-3-(4-trifluoromethyl-pyridin-3-ylmethylthio)-2-isoxazolineas a yellow oily substance.

¹H-NMR [CDCl₃/TMS, δ (ppm)]:

8.98 (1H,s), 8.70 (1H,d), 7.51 (1H,d), 4.47 (2H,s), 2.79 (2H,s), 1.43(6H,s)

PREPARATION EXAMPLE 38 Production of5,5-dimethyl-3-(4-trifluoromethyl-pyridin-3-ylmethylsulfonyl)-2-isoxazoline(Present Compound No. 7-0001) and5,5-dimethyl-3-(4-trifluoromethyl-pyridine-N-oxide-3-ylmethylsulfonyl)-2-isoxazoline(Present Compound No. 7-0002)

0.77 g of m-chloroperbenzoic acid (purity: 70%, 4.5 mmoles) was added,with ice-cooling, to a solution of 0.45 g (1.6 mmoles) of5,5-dimethyl-3-(4-trifluoromethyl-pyridin-3-ylmethylthio)-2-isoxazolinedissolved in 20 ml of chloroform. The mixture was stirred for 1 hour andthen at room temperature for 12 hours to give rise to a reaction. Afterconfirmation of the completion of the reaction, the reaction mixture waspoured into water, followed by extraction with chloroform. The resultingorganic layer was washed with an aqueous sodium hydrogensulfitesolution, an aqueous sodium hydrogencarbonate solution, water and anaqueous sodium chloride solution in this order and then dried overanhydrous magnesium sulfate. The resulting solution was subjected tovacuum distillation to remove the solvent contained therein. The residuewas purified by silica gel column chromatography (developing solvent:hexane-ethyl acetate mixed solvent) to obtain 0.06 g (yield: 12.0%) of5,5-dimethyl-3-(4-trifluoromethyl-pyridin-3-ylmethylsulfonyl)-2-isoxazolineas light yellow crystals (melting point: 77.0 to 80.0° C.) and 0.12 g(yield: 23.1%) of5,5-dimethyl-3-(4-trifluoromethyl-pyridin-N-oxide-3-ylmethylsulfonyl)-2-isoxazolineas white crystals (melting point: 114.0 to 116.0° C.).

5,5-Dimethyl-3-(4-trifluoromethyl-pyridin-3-ylmethylsulfonyl)-2-isoxazoline

¹H-NMR [CDCl₃/TMS, δ (ppm)]:

8.98 (1H,s), 8.84 (1H,d), 7.64 (1H,d), 4.92 (2H,s), 3.09 (2H,s), 1.52(6H,s)

5,5-Dimethyl-3-(4-trifluoromethyl-pyridin-N-oxide-3-ylmethylsulfonyl)-2-isoxazoline

¹H-NMR [CDCl₃/TMS, δ (ppm)]:

8.50 (1H,s), 8.25 (1H,d), 7.59 (1H,d), 4.81 (2H,s), 3.12 (2H,s), 1.53(6H,s)

PREPARATION EXAMPLE 39 Production of5,5-dimethyl-[(4-methoxy-6-trifluoromethylpyrimidin-5-yl)-methylthio]-2-isoxazoline(Present Compound No. 8-0002)

0.32 g of sodium hydrosulfide (purity: 70%, 4.00 mmoles) was added, atroom temperature, to a solution of 0.35 g (2.00 mmoles) of5,5-dimethyl-3-methylsulfonyl-2-isoxazoline dissolved in 10 ml ofdimethylformamide. The mixture was stirred for 2 hours. To the reactionmixture were added 0.28 g (2.00 mmoles) of anhydrous potassiumcarbonate, 0.31 g (2.00 mmoles) of Rongalit and 0.45 g (2.00 mmoles) of5-chloromethyl-4-methoxy-6-trifluoromethylpyrimidine. The resultingmixture was stirred at room temperature for 2 hours to give rise to areaction. After confirmation of the completion of the reaction, thereaction mixture was poured into water, followed by extraction withethyl acetate. The resulting organic layer was washed with water and anaqueous sodium chloride solution and then dried over anhydrous magnesiumsulfate. The resulting solution was subjected to vacuum distillation toremove the solvent contained therein. The residue was purified by silicagel column chromatography to obtain 0.55 g (yield: 85.9%) of5,5-dimethyl-[(4-methoxy-6-trifluoromethylpyrimidin-5-yl)-methylthio]-2-isoxazoline.

¹H-NMR (CDCl₃/TMS, δ (ppm)]:

8.81 (1H,s), 4.44 (2H,d), 4.12 (3H,s), 2.81 (2H,s), 1.45 (6H,s)

PREPARATION EXAMPLE 40 Production of5,5-dimethyl-[(4-methoxy-6-trifluoromethylpyrimidin-5-yl)-methylsulfonyl]-2-isoxazoline(Present Compound No. 8-0001)

1.05 g of m-chloroperbenzoic acid (purity: 70%, 4.28 mmoles) was added,with ice-cooling, to a solution of 0.55 g (1.71 mmoles) of5,5-dimethyl-[(4-methoxy-6-trifluoromethylpyrimidin-5-yl)-methylthio]-2-isoxazolinedissolved in 20 ml of chloroform. The mixture was stirred for 1 hour andthen at room temperature for 4 hours to give rise to a reaction. Afterthe completion of the reaction, the reaction mixture was poured intowater, followed by extraction with chloroform. The resulting organiclayer was washed with an aqueous sodium hydrogensulfite solution, anaqueous sodium hydrogencarbonate solution and an aqueous sodium chloridesolution in this order and then dried over anhydrous magnesium sulfate.The resulting solution was subjected to vacuum distillation to removethe solvent contained therein. The residue was purified by silica gelcolumn chromatography to obtain 0.45 g (yield: 75.0%) of5,5-dimethyl-[(4-methoxy-6-trifluoromethylpyrimidin-5-yl)-methylsulfonyl]-2-isoxazolineas white feather-like crystals (melting point: 175 to 176° C.).

¹H-NMR [CDCl₃/TMS, δ (ppm)]:

8.89 (1H,s), 5.00 (2H,d), 4.11 (3H,s), 3.11 (2H,s), 1.53 (6H,s)

PREPARATION EXAMPLE 41 Production of3-(5,5-dimethyl-2-isoxazolin-3-ylthiomethyl)-2-trifluoromethyl-6,7-dihydro-5H-pyrazolo[5,1-b][1,3]oxazine(Present Compound No. 3-0033)

A solution of 0.82 g (2.3 mmoles) of3-[5-chloro-1-(3-hydroxypropyl)-3-trifluoromethyl-1H-pyrazol-4-ylmethylthio]-5,5-dimethyl-2-isoxazoledissolved in 5 ml of N,N-dimethylformamide was dropwise added to asuspension of 0.11 g (2.8 mmoles) of sodium hydride in 15 ml ofN,N-dimethylformamide. After the completion of the dropwise addition,the resulting mixture was stirred at room temperature for 30 minutes,then heated to 100° C., and stirred for 1 hour to give rise to areaction. After confirmation of the completion of the reaction, thereaction mixture was poured into water, followed by extraction withethyl acetate. The resulting organic layer was washed with an aqueouscitric acid solution and an aqueous sodium chloride solution, and thendried over magnesium sulfate. The resulting solution was subjected tovacuum distillation to obtain 0.77 g (yield: 100%) of3-(5,5-dimethyl-2-isoxazolin-3-ylthiomethyl)-2-trifluoromethyl-6,7-dihydro-5H-pyrazolo[5,1-b][1,3]oxazine.

¹H-NMR [CDCl₃/TMS, δ (ppm)]:

4.37 (2H,t), 4.19 (2H,t), 4.15 (2H,s), 2.80 (2H,s), 2.31 (2H,m), 1.42(6H,s)

PREPARATION EXAMPLE 42 Production of3-(5,5-dimethyl-2-isoxazolin-3-ylsulfonylmethyl)-2-trifluoromethyl-6,7-dihydro-5H-pyrazolo[5,1-b][1,3]oxazine(Present Compound No. 3-0019)

1.25 g of m-chloroperbenzoic acid (purity: 70%, 5.1 mmoles) was added,with ice-cooling, to a solution of 0.77 g (2.3 mmoles) of3-(6,7-dihydro-3-trifluoromethyl-5H-pyrazolo[5,1-b][1,3]oxazin-4-yl-methylthio)-5,5-dimethyl-2-isoxazolinedissolved in 20 ml of chloroform. The mixture was stirred for 1 hour andthen at room temperature for 12 hours to give rise to a reaction. Afterconfirmation of the completion of the reaction, the reaction mixture waspoured into water, followed by extraction with chloroform. The resultingorganic layer was washed with an aqueous sodium hydrogensulfitesolution, an aqueous sodium hydrogencarbonate solution, water and anaqueous sodium chloride solution in this order and then dried overanhydrous magnesium sulfate. The resulting solution was subjected tovacuum distillation to remove the solvent contained therein. The residuewas purified by silica gel column chromatography to obtain 0.36 g(yield: 43%) of3-(5,5-dimethyl-2-isoxazolin-3-ylsulfonylmethyl)-2-trifluoromethyl-6,7-dihydro-5H-pyrazolo[5,1-b][1,3]oxazineas a white powder (melting point: 151.0 to 152.0° C.).

¹H-NMR [CDCl₃/TMS, δ (ppm)]:

4.47 (2H,s), 4.40 (2H,t), 4.23 (2H,t), 3.09 (2H,s), 2.34 (2H,m), 1.50(6H,s)

PREPARATION EXAMPLE 43 Production of3-(5-chloro-1-methyl-3-trifluoromethylpyrazol-4-ylmehylthio)-5,5-dimethyl-2-isoxazoline(Present Compound No. 3-0186)

5.59 g of sodium hydrosulfide hydrate (purity: 70%, 69.8 mmoles) wasadded, at room temperature, to a solution of 6.84 g (35.8 mmoles) of5,5-dimethyl-3-ethanesulfonyl-2-isoxazoline dissolved in 200 ml ofN,N-dimethylformamide. The mixture was stirred for 1 hour. To thereaction mixture, were added 4.94 g (35.8 mmoles) of anhydrous potassiumcarbonate, 5.51 g (35.8 mmoles) of Rongalit and further 9.46 g (34.1mmoles) of4-bromomethyl-5-chloro-1-methyl-3-trifluoromethyl-1H-pyrazole. Theresulting mixture was stirred at room temperature over one night to giverise to a reaction. After confirmation of the completion of thereaction, the reaction mixture was poured into water, followed byextraction with ethyl acetate. The resulting organic layer was washedwith water and an aqueous sodium chloride solution in this order andthen dried over anhydrous magnesium sulfate. The resulting solution wassubjected to vacuum distillation to remove the solvent containedtherein. The residue was purified by silica gel column chromatography toobtain 8.97 g (yield: 80.3%) of3-(5-chloro-1-methyl-3-trifluormethylpyrazol-4-ylmethylthio)-5,5-dimethyl-2-isoxazoline.

PREPARATION EXAMPLE 44 Production of3-(5-chloro-1-methyl-3-trifluoromethylpyrazol-4-ylmethanesulfonyl)-5,5-dimethyl-2-isoxazoline(Present Compound No. 3-0039)

16.87 g of m-chloroperbenzoic acid (purity: 70%, 68.4 mmoles) was added,with ice-cooling, to a solution of 8.97 g (27.4 mmoles) of3-(5-chloro-1-methyl-3-trifluoromethylpyrazol-4-ylmethylthio)-5,5-dimethyl-2-isoxazolinedissolved in 300 ml of chloroform. The mixture was stirred for 1 hourand then at room temperature over one night to give rise to a reaction.After the completion of the reaction, the reaction mixture was pouredinto water, followed by extraction with chloroform. The resultingorganic layer was washed with an aqueous sodium hydrogensulfitesolution, an aqueous sodium hydrogencarbonate solution, water and anaqueous sodium chloride solution in this order and then dried overanhydrous magnesium sulfate. The resulting solution was subjected tovacuum distillation to remove the solvent contained therein. The solidthus obtained was washed with n-hexane to obtain 9.36 g (yield: 95.1%)of3-(5-chloro-1-methyl-3-trifluoromethylpyrazol-4-ylmethanesulfonyl)-5,5-dimethyl-2-isoxazolineas white powder (melting point: 115.0 to 116.0° C.).

¹H-NMR [CDCl₃/TMS, δ (ppm)]:

4.63 (2H,s), 3.95 (3H,s), 3.10 (2H,s), 1.52 (6H,s)

PREPARATION EXAMPLE 45 Production of3-(5-difluoromethoxy-1-methyl-3-trifluoromethyl-1H-pyrazol-4-ylmethylthio-5,5-dimethyl-2-isoxazoline(Present Compound No. 3-0187)

49.4 g (0.88 mol) of powdery potassium hydroxide and 0.94 g (2.9 mmol)of tetra-n-butylammonium bromide were added at room temperature to asolution of 90.3 g (0.29 mole) of3-(5-hydroxy-1-methyl-3-trifluoromethyl-1H-pyrazol-4-ylmethylthio)-5,5-dimethyl-2-isoxazolinedissolved in 1000 ml of tetrahydrofuran. While cooling the system to 20°C. or lower, an excess amount of chlorodifluoromethane was introduced soas to have the system saturated. Thereafter, the reaction mixture wasstirred at room temperature for 17 hours. After confirmation of thecompletion of the reaction, the reaction solution was poured into icewater, followed by extraction with ethyl acetate. The resulting organiclayer was washed with water and a saturated aqueous sodium chloridesolution in this order, and then dried over anhydrous magnesium sulfate.The resulting solution was subjected to vacuum distillation to removethe solvent contained therein. The residue was purified by silica gelchromatography to obtain 66.6 g (purity: 85%, yield; 54.0%) of3-(5-difluoromethoxy-1-methyl-3-trifluoro-1H-pyrazol-4-ylmethylthio)-5,5-dimethyl-2-isoxazoline.

PREPARATION EXAMPLE 46 Production of3-(5-difluoromethoxy-1-methyl-3-trifluoromethyl-1H-pyrazol-4-ylmethanesulfonyl)-5,5-dimethyl-2-isoxazoline(Present Compound No. 3-0188)

157.6 g of m-chloroperbenzoic acid (purity: 70%, 0.64 mole) was added,with ice-cooling, to a solution of 56.5 g (0.16 mole) of3-(5-difluoromethoxy-1-methyl-3-trifluoromethyl-1H-pyrazol-4-ylmethylthio)-5,5-dimethyl-2-isoxazolinedissolved in 1000 ml of chloroform. The mixture was stirred at roomtemperature for 4 hours to give rise to a reaction. After the completionof the reaction, the reaction solution was filtrated to remove insolublematters. The filtrate thus obtained was poured into ice water, followedby extraction with chloroform. The resulting organic layer was washedwith a 10% aqueous sodium hydroxide solution, water, an aqueous sodiumhydrogensulfite solution, and a saturated aqueous sodium chloridesolution in this order and then dried over anhydrous magnesium sulfate.The resulting solution was subjected to vacuum distillation to removethe solvent contained therein. The residue was washed with n-hexane toobtain 52.7 g (yield: 86.0%) of3-(5-difluoromethoxy-1-methyl-3-trifluoromethyl-1H-pyrazol-4-ylmethanesulfonyl)-5,5-dimethyl-2-isoxazolineas white crystals (melting point: 129.0 to 130.0° C.).

¹H-NMR [CDCl₃/TMS, δ (ppm)]:

6.83 (1H,t,J=71.9 Hz), 4.60 (2H,s), 3.88 (3H,s), 3.11 (2H,s), 1.52(6H,s)

PREPARATION EXAMPLE 47 Production of3-(5-difluoromethoxy-1-ethyl-3-trifluoromethyl-1H-pyrazol-4-ylmethylthio-5,5-dimethyl-2-isoxazoline(Present Compound No. 3-0189)

30.1 g (536.6 mmol) of powdery potassium hydroxide and 0.5 g oftetra-n-butylammonium bromide were added to a solution of 34.7 g (107.3mmoles) of3-(1-ethyl-5-hydroxy-3-trifluoromethyl-1H-pyrazol-4-ylmethylthio)-5,5-dimethyl-2-isoxazolinedissolved in 100 ml of dichloromethane. An excess amount ofchlorodifluoromethane was introduced so as to have the system saturated.Thereafter, the reaction mixture was stirred for 3 hours. Afterconfirmation of the completion of the reaction, the reaction solutionwas poured into water, followed by extraction with chloroform. Theresulting organic layer was washed with water and a saturated aqueoussodium chloride solution in this order, and then dried over anhydrousmagnesium sulfate. The resulting solution was subjected to vacuumdistillation to remove the solvent contained therein. The residue waspurified by silica gel chromatography to obtain 26.3 g (yield; 65.5%) of3-(5-difluoromethoxy-1-ethyl-3-trifluoro-1H-pyrazol-4-ylmethylthio)-5,5-dimethyl-2-isoxazoline.

PREPARATION EXAMPLE 48 Production of3-(5-difluoromethoxy-1-ethyl-3-trifluoromethyl-1H-pyrazol-4-ylmethanesulfonyl)-5,5-dimethyl-2-isoxazoline(Present Compound No. 3-0190)

30.5 g of m-chloroperbenzoic acid (purity: 70%, 123.9 mmoles) was added,with ice-cooling, to a solution of 18.5 g (49.6 mmoles) of3-(5-difluoromethoxy-1-ethyl-3-trifluoromethyl-1H-pyrazol-4-ylmethylthio)-5,5-dimethyl-2-isoxazolinedissolved in 200 ml of chloroform. The mixture was stirred at roomtemperature over one night to give rise to a reaction. After thecompletion of the reaction, the reaction solution was poured into water,followed by extraction with chloroform. The resulting organic layer waswashed with an aqueous sodium hydrogensulfite solution, an aqueoussodium hydrogencarbonate solution, water, and an aqueous sodium chloridesolution in this order and then dried over anhydrous magnesium sulfate.The resulting solution was subjected to vacuum distillation to removethe solvent contained therein. The residue was washed with n-hexane toobtain 19.3 g (yield: 96.0%) of3-(5-difluoromethoxy-1-ethyl-3-trifluoromethyl-1H-pyrazol-4-ylmethanesulfonyl)-5,5-dimethyl-2-isoxazolineas white powder (melting point: 98 to 100° C.).

¹H-NMR [CDCl₃/TMS, δ (ppm)]:

6.83 (1H,t,J=72.0 Hz), 4.60 (2H,s), 4.19 (2H,q), 3.11 (2H,s), 1.52(6H,s), 1.49 (3H,t)

PREPARATION EXAMPLES OF INTERMEDIATES REFERENCE EXAMPLE 1 Production of3-chloro-5,5-dimethyl-2-isoxazoline

534.0 g (4.0 moles) of N-chlorosuccinimide was gradually added, at 65 to70° C., to a solution of 182.7 g (2.05 moles) of glyoxylic acid aldoximedissolved in 2 liters of 1,2-dimethoxyethane. The mixture was refluxedfor 1 hour with heating. Thereto were added, with ice-cooling, 1,440.0 g(14.4 moles) of potassium hydrogencarbonate and 10 ml of water. Then,360.0 g (6.4 moles) of 2-methylpropene was added. The resulting mixturewas stirred at room temperature for 24 hours to give rise to a reaction.The reaction mixture was poured into water, followed by extraction withdiisopropyl ether. The resulting organic layer was washed with water andan aqueous sodium chloride solution in this order and then dried overanhydrous magnesium sulfate. The resulting solution was subjected tovacuum distillation to remove the solvent contained therein, to obtain107.7 g (yield: 40.0%) of 3-chloro-5,5-dimethyl-2-isoxazoline as ayellow viscous liquid.

¹H-NMR [CDCl₃/TMS, δ (ppm)]:

2.93 (2H,s), 1.47 (6H,s)

REFERENCE EXAMPLE 2 Production of3-chloro-5-ethyl-5-methyl-2-isoxazoline

61.9 g (463.4 mmoles) of N-chlorosuccinimide was gradually added, at 60°C., to a solution of 20.6 g (231.7 mmoles) of glyoxylic acid aldoximedissolved in 500 ml of 1,2-dimethoxyethane. After the addition, themixture was refluxed for 10 minutes with heating. Thereto were added,with ice-cooling, 50 ml (463.4 mmoles) of 2-methyl-1-butene, 98.9 g(1,622 mmoles) of potassium hydrogencarbonate and 10 ml of water. Theresulting mixture was stirred for 12 hours to give rise to a reaction.The reaction mixture was poured into water, followed by extraction withn-hexane. The resulting organic layer was washed with water and anaqueous sodium chloride solution in this order and then dried overanhydrous magnesium sulfate. The resulting solution was subjected tovacuum distillation to remove the solvent contained therein, to obtain13.9 g (yield: 40.6%) of 3-chloro-5-ethyl-5-methyl-2-isoxazoline as ayellow viscous liquid.

¹H-NMR [CDCl₃/TMS, δ (ppm)]:

2.91 (2H, ABq, J=17.0, Δv=46.1 Hz), 1.73 (2H,q), 1.42 (3H,s), 0.96(3H,t)

REFERENCE EXAMPLE 3 Production of3-benzylthio-5,5-dimethyl-2-isoxazoline

3.2 g (23.2 mmoles) of anhydrous potassium carbonate and 3.0 g (22.5mmoles) of 3-chloro-5,5-dimethyl-2-isoxazoline were added, in a nitrogenatmosphere, to a solution of 2.8 g (22.5 mmoles) of benzylmercaptandissolved in 50 ml of N,N-dimethylformamide. The mixture was stirred at100° C. for 2 hours to give rise to a reaction. After the completion ofthe reaction, the reaction mixture was poured into water, followed byextraction with ethyl acetate. The resulting organic layer was washedwith water and an aqueous sodium chloride solution in this order andthen dried over anhydrous magnesium sulfate. The resulting solution wassubjected to vacuum distillation to remove the solvent containedtherein. The residue was purified by silica gel column chromatography toobtain 3.1 g (yield: 62.0%) of 3-benzylthio-5,5-dimethyl-2-isoxazolineas a yellow oily substance (n_(D) ²⁰=1.5521).

¹H-NMR [CDCl₃/TMS, δ (ppm)]:

7.24-7.39 (5H,m), 4.26 (2H,s), 2.77 (2H,s), 1.40 (6H,s)

REFERENCE EXAMPLE 4 Production of3-(2,6-difluorobenzylsulfinyl)-5-ethyl-5-methyl-2-isoxazoline

4.6 g of m-chloroperbenzoic acid (purity: 70%, 18.8 mmoles) was added,with ice-cooling, to a solution of 4.1 g (15.0 mmoles) of3-(2,6-difluorobenzylthio)-5-ethyl-5-methyl-2-isoxazoline dissolved in50 ml of chloroform. The mixture was stirred for 1 hour and then at roomtemperature for 12 hours to give rise to a reaction. After thecompletion of the reaction. the reaction mixture was poured into water,followed by extraction with chloroform. The resulting organic layer waswashed with an aqueous sodium hydrogensulfite solution, an aqueoussodium hydrogencarbonate solution, water and an aqueous sodium chloridesolution in this order and then dried over anhydrous magnesium sulfate.The resulting solution was subjected to vacuum distillation to removethe solvent contained therein. The residue was purified by silica gelcolumn chromatography (developing solvent: hexane-ethyl acetate mixedsolvent) to obtain 1.5 g (yield: 34.8%) of3-(2,6-difluorobenzylsulfinyl)-5-ethyl-5-methyl-2-isoxazoline as a whitepowder (melting point: 30° C. or less).

¹H-NMR [CDCl₃/TMS, δ (ppm)]:

7.39-7.28 (1H,m), 7.03-6.94 (2H,m), 4.38 (2H,s), 3.04 (1H, ABq, J=17.2,Δv=85.7 Hz), 3.12 (1H,s), 1.75 (2H,m), 1.44 (3H,S)+1.41 (3H,s), 0.97(3H,m)

REFERENCE EXAMPLE 5 Production of3-(2,6-difluorobenzylsulfonyl)-5-ethyl-5-methyl-2-isoxazoline

1.0 g of m-chloroperbenzoic acid (purity: 70%, 4.1 mmoles) was added,with ice-cooling, to a solution of 0.8 g (2.8 mmoles) of3-(2,6-difluorobenzylsulfinyl)-5-ethyl-5-methyl-2-isoxazoline dissolvedin 50 ml of chloroform. The mixture was stirred for 1 hour and then atroom temperature for 12 hours to give rise to a reaction. After thecompletion of the reaction. the reaction mixture was poured into water,followed by extraction with chloroform. The resulting organic layer waswashed with an aqueous sodium hydrogensulfite solution, an aqueoussodium hydrogencarbonate solution, water and an aqueous sodium chloridesolution in this order and then dried over anhydrous magnesium sulfate.The resulting solution was subjected to vacuum distillation to removethe solvent contained therein. The residue was purified by silica gelcolumn chromatography (developing solvent: hexane-ethyl acetate mixedsolvent) to obtain 0.6 g (yield: 75.0%) of3-(2,6-difluorobenzylsulfonyl)-5-ethyl-5-methyl-2-isoxazoline as a whitepowder (melting point: 64 to 65° C.).

¹H-NMR [CDCl₃/TMS, δ (ppm)]:

7.36-7.46 (1H,m), 6.98-7.04 (2H,m), 4.73 (2H,s), 3.04 (2H, ABq, J=17.2,Δv=51.1 Hz), 1.77 (2H,q), 1.46 (3H,s), 0.97 (3H,t)

REFERENCE EXAMPLE 6 Production of5,5-dimethyl-3-methylsulfonyl-2-isoxazoline

1.0 kg of an aqueous sodium methanethiolate solution (content: 15%, 2.14mmoles) was dropwise added, with ice-cooling, to a solution of 143.0 g(1.07 moles) of 3-chloro-5,5-dimethyl-2-isoxazoline dissolved in 500 mlof N,N-dimethylformamide. The mixture was stirred at room temperaturefor 12 hours to give rise to a reaction. After the completion of thereaction, the reaction mixture was poured into water, followed byextraction with ethyl acetate. The resulting organic layer was washedwith an aqueous sodium chloride solution and then dried over anhydrousmagnesium sulfate. The resulting solution was subjected to vacuumdistillation to remove the solvent contained therein, to obtain 115.0 g(yield: 74.1%) of 5,5-dimethyl-3-methylthio-2-isoxazoline. This residue(741.2 mmoles) was dissolved in 1 liter of chloroform. Thereto wasadded, with ice-cooling, 392.0 g of m-chloroperbenzoic acid (purity:70%, 1.59 moles). The resulting mixture was stirred for 1 hour and thenat room temperature for 12 hours to give rise to a reaction. After thecompletion of the reaction, the separated m-chloroperbenzoic acid wasremoved by filtration. The resulting filtrate was washed with an aqueoussodium hydrogensulfite solution, water, an aqueous sodiumhydrogencarbonate solution and an aqueous sodium chloride solution inthis order and then dried over anhydrous magnesium sulfate. Theresulting solution was subjected to vacuum distillation to remove thesolvent contained therein. The residue was washed with diisopropyl etherto obtain 77.6 g (yield: 59.1%) of5,5-dimethyl-3-methylsulfonyl-2-isoxazoline as a white powder (meltingpoint: 82 to 84° C.).

¹H-NMR [CDCl₃/TMS, δ (ppm)]:

3.26 (3H,s), 3.12 (2H,s), 1.51 (6H,s)

REFERENCE EXAMPLE 7 Production of 5,5-dimethyl-3-ethylthio-2-isoxazoline

1,500 ml of an aqueous solution containing 560.0 g (9.0 moles) of ethylmercaptan and 360.0 g (9.0 moles) of sodium hydroxide was added to asolution containing 3-chloro-5,5-dimethyl-2-isoxazoline. The mixture wasstirred at 60 to 70° C. for 16 hours to give rise to a reaction. Afterconfirmation of the completion of the reaction, the reaction mixture waspoured into water, followed by extraction with ethyl acetate. Theresulting organic layer was washed with water and an aqueous sodiumchloride solution and then dried over anhydrous magnesium sulfate. Theresulting solution was subjected to vacuum distillation to remove thesolvent contained therein, to obtain 270.0 g of crude5,5-dimethyl-3-ethylthio-2-isoxazoline as a dark red oily substance.

REFERENCE EXAMPLE 8 Production of5,5-dimethyl-3-ethylsulfonyl-2-isoxazoline

270.0 g (1.7 moles) of crude oily 5,5-dimethyl-3-ethylthio-2-isoxazolinewas dissolved in 1.0 liter of chloroform. Thereto was added, withice-cooling, 1,050 g of m-chloroperbenzoic acid (purity: 70%, 6.1moles). The resulting mixture was stirred for 1 hour and then at roomtemperature for 12 hours to give rise to a reaction. After confirmationof the completion of the reaction, the separated m-chloroperbenzoic acidwas removed by filtration. The resulting filtrate was washed with anaqueous sodium hydrogensulfite solution, an aqueous sodiumhydrogencarbonate solution, water and an aqueous sodium chloridesolution in this order and then dried over anhydrous magnesium sulfate.The resulting solution was subjected to vacuum distillation to removethe solvent contained therein. The residue was washed with n-hexane toobtain 133.6 g (yield: 65.4%) of5,5-dimethyl-3-ethylsulfonyl-2-isoxazoline as a white powder.

REFERENCE EXAMPLE 9 Production of1-phenyl-3-trifluoromethyl-1H-pyrazol-5-ol

20 g (184.9 mmoles) of phenylhydrazine and 4 ml of concentratedhydrochloric acid were added to a solution of 34.1 g (184.9 mmoles) ofethyl trifluoroacetoacetate dissolved in 500 ml of ethanol. The mixturewas refluxed for 1 hour with heating, to give rise to a reaction. Afterthe completion of the reaction, the reaction mixture was subjected tovacuum distillation to remove the most part of the solvent containedtherein. The residue was mixed with water to precipitate crystals. Thecrystals were collected by filtration, washed with water until thefiltrate became neutral, and dried to obtain 37.1 g (yield: 87.9%) of1-phenyl-3-trifluoromethyl-1H-pyrazol-5-ol as ocherous crystals.

¹H-NMR [CDCl₃/TMS, δ (ppm)]:

7.68-7.41 (5H,m), 5.86 (1H,s), 3.71 (1H,s)

REFERENCE EXAMPLE 10 Production of5-chloro-1-phenyl-3-trifluoromethyl-1H-pyrazole-4-carboaldehyde

33.6 g (219.1 mmoles) of phosphorus oxychloride was added to 7.7 g(105.2 mmoles) of N,N-dimethylformamide with ice-cooling. Thereto wasadded, at room temperature, 20 g (87.7 mmoles) of1-phenyl-3-trifluoromethyl-1H-pyrazol-5-ol. The resulting mixture wasrefluxed for 1 hour with heating, to give rise to a reaction. After thecompletion of the reaction, the reaction mixture was poured into waterwith ice-cooling, followed by extraction with chloroform. The resultingorganic layer was washed with an aqueous sodium hydrogencarbonatesolution and an aqueous sodium chloride solution in this order and thendried over anhydrous magnesium sulfate. The resulting solution wassubjected to vacuum distillation to remove the solvent containedtherein. The residue was purified by silica gel column chromatography(developing solvent: hexane-ethyl acetate mixed solvent) to obtain 19.1g (yield: 79.1%) of5-chloro-1-phenyl-3-trifluoromethyl-1H-pyrazole-4-carboaldehyde as whitecrystals.

¹H-NMR [CDCl₃/TMS, δ (ppm)]:

10.06 (1H,s), 7.57 (5H,s)

REFERENCE EXAMPLE 11 Production of(5-chloro-1-phenyl-3-trifluoromethyl-1H-pyrazol-4-yl)-methanol

A solution of 0.21 g (5.5 mmoles) of lithium aluminum hydride dissolvedin 70 ml of THF was cooled to −30° C. Thereto was gradually added asolution of 3 g (10.9 mmoles) of5-chloro-1-phenyl-3-trifluoromethyl-1H-pyrazole-4-carboaldehydedissolved in 30 ml of tetrahydrofuran. The resulting mixture was stirredat −30° C. for 30 minutes to give rise to a reaction. After thecompletion of the reaction, ethyl acetate was added, followed bystirring. Then, water was added, followed by stirring for a while. Thereaction mixture was filtered under vacuum. The filtrate was extractedwith ethyl acetate. The resulting organic layer was washed with anaqueous sodium chloride solution and then dried over anhydrous magnesiumsulfate. The resulting solution was subjected to vacuum distillation toremove the solvent contained therein, to obtain 3.0 g (yield: 99.9%) of(5-chloro-1-phenyl-3-trifluoromethyl-1H-pyrazol-4-yl)-methanol as whitecrystals.

¹H-NMR [CDCl₃/TMS, δ (ppm)]:

7.54-7.51 (5H,m), 4.71 (2H,d) 1.79 (1H,b)

REFERENCE EXAMPLE 12 Production of4-bromomethyl-5-chloro-1-phenyl-3-trifluoromethyl-1H-pyrazole

A solution of 3.0 g (10.9 mmoles) of(5-chloro-1-phenyl-3-trifluoromethyl-1H-pyrazol-4-yl)-methanol dissolvedin 60 ml of diethyl ether was cooled to −10° C. Thereto was added 1.0 g(3.8 mmoles) of phosphorus tribromide. The mixture was stirred at roomtemperature for 1 hour to give rise to a reaction. After the completionof the reaction, the reaction mixture was poured into water, followed byextraction with ethyl acetate. The resulting organic layer was washedwith an aqueous sodium chloride solution and then dried over anhydrousmagnesium sulfate. The resulting solution was subjected to vacuumdistillation to remove the solvent contained therein, to obtain 3.6 g(yield: 95.8%) of4-bromomethyl-5-chloro-1-phenyl-3-trifluoromethyl-1H-pyrazole as whitecrystals.

¹H-NMR [CDCl₃/TMS, δ (ppm)]:

7.58-7.48 (5H,m), 4.48 (2H,s)

REFERENCE EXAMPLE 13 Production of5-fluoro-1-phenyl-3-trifluoromethyl-1H-pyrazole-4-carboaldehyde

10.5 g (180.2 mmoles) of potassium fluoride was added to a solution of33.0 g (120.1 mmoles) of5-chloro-1-phenyl-3-trifluoromethyl-1H-pyrazole-4-carboaldehydedissolved in 500 ml of dimethyl sulfoxide. The mixture was stirred at100° C. for 2 hours to give rise to a reaction. After the completion ofthe reaction, the reaction mixture was poured into water, followed byextraction with ethyl acetate. The resulting organic layer was washedwith an aqueous sodium chloride solution and then dried over anhydrousmagnesium sulfate. The resulting solution was subjected to vacuumdistillation to remove the solvent contained therein. The residue waspurified by silica gel column chromatography (developing solvent:hexane-ethyl acetate mixed solvent) to obtain 26.5 g (yield: 85.0%) of5-fluoro-1-phenyl-3-trifluoromethyl-1H-pyrazole-4-carboaldehyde.

¹ H-NMR [CDCl₃/TMS, δ (ppm)]:

9.96 (1H,s), 7.68-7.51 (5H,m)

REFERENCE EXAMPLE 14 Production of(5-fluoro-1-phenyl-3-trifluoromethyl-1H-pyrazol-4-yl)-methanol

To a solution of 1.6 g (41.0 mmoles) of sodium borohydride dissolved in300 ml of methanol was added, with ice-cooling, a solution of 26.5 g(102.5 mmoles) of5-fluoro-1-phenyl-3-trifluoromethyl-1H-pyrazole-4-carboaldehydedissolved in 200 ml of methanol. The resulting mixture was stirred at 0°C. for 30 minutes to give rise to a reaction. After the completion ofthe reaction, the reaction mixture was poured into water, followed byextraction with ethyl acetate. The resulting organic layer was washedwith an aqueous sodium chloride solution and then dried over anhydrousmagnesium sulfate. The resulting solution was subjected to vacuumdistillation to remove the solvent contained therein, to obtain 28.5 g(yield: 100%) of(5-fluoro-1-phenyl-3-trifluoromethyl-1H-pyrazol-4-yl)-methanol.

¹H-NMR [CDCl₃/TMS, δ (ppm)]:

7.65-7.41 (5H,m), 4.68 (2H,d), 1.73 (1H,t)

REFERENCE EXAMPLE 15 Production of4-bromomethyl-5-fluoro-1-phenyl-3-trifluoromethyl-1H-pyrazole

A solution of 27.5 g (105.7 mmoles) of(5-fluoro-1-phenyl-3-trifluoromethyl-1H-pyrazol-4-yl)-methanol dissolvedin 300 ml of diethyl ether was cooled to 0° C. Thereto was added 10.0 g(37.0 mmoles) of phosphorus tribromide. The mixture was stirred at roomtemperature for 2 hours to give rise to a reaction. After the completionof the reaction, the reaction mixture was poured into water, followed byextraction with diethyl ether. The resulting organic layer was washedwith an aqueous sodium chloride solution and then dried over anhydrousmagnesium sulfate. The resulting solution was subjected to vacuumdistillation to remove the solvent contained therein, to obtain 30.3 g(yield: 88.8%) of4-bromomethyl-5-fluoro-1-phenyl-3-trifluoromethyl-1H-pyrazole.

¹H-NMR [CDCl₃/TMS, δ (ppm)]:

7.66-7.42 (5H,m), 4.44 (2H,s)

REFERENCE EXAMPLE 16 Production of1-tert-butyl-3-trifluoromethyl-1H-pyrazol-5-ol

373.8 g (3.0 moles) of tert-butylhydrazine hydrochloride and 50 ml ofconcentrated hydrochloric acid were added to a solution of 552.3 g (3.0moles) of ethyl trifluoroacetoacetate dissolved in 1,500 ml of ethanol.The mixture was refluxed for 2 days with heating, to give rise to areaction. After the completion of the reaction, the reaction mixture wassubjected to vacuum distillation to remove the most part of the solventcontained therein. The residue was poured into water, followed byextraction with ethyl acetate. The resulting organic layer was washedwith water and an aqueous sodium chloride solution in this order andthen dried over anhydrous magnesium sulfate. The resulting solution wassubjected to vacuum distillation to remove the solvent containedtherein. The residue was washed with n-hexane to obtain 369.0 g (yield:59.1%) of 1-tert-butyl-3-trifluoromethyl-1H-pyrazol-5-ol as a whitepowder.

REFERENCE EXAMPLE 17 Production of1-tert-butyl-5-chloro-3-trifluoromethyl-1H-pyrazole-4-carboaldehyde

462.0 g (3.0 moles) of phosphorus oxychloride was added to 87.7 g (1.2moles) of N,N-dimethylformamide with ice-cooling. Thereto was added, atroom temperature, 208.2 g (1.0 moles) of1-tert-butyl-3-trifluoromethyl-1H-pyrazol-5-ol. The resulting mixturewas refluxed for 10 hours with heating, to give rise to a reaction.After the completion of the reaction, the reaction mixture was pouredinto water, followed by extraction with chloroform. The resultingorganic layer was washed with water, a 5% aqueous sodium hydroxidesolution and water in this order and then dried over anhydrous magnesiumsulfate. The resulting solution was subjected to vacuum distillation toremove the solvent contained therein. The residue was purified by silicagel column chromatography (developing solvent: hexane-ethyl acetatemixed solvent) to obtain 131.5 g (yield: 21.7%) of1-tert-butyl-5-chloro-3-trifluoromethyl-1H-pyrazole-4-carboaldehyde aswhite crystals.

¹H-NMR [CDCl₃/TMS, δ (ppm)]:

9.97 (1H,d), 1.76 (9H,s)

REFERENCE EXAMPLE 18 Production of(1-tert-butyl-5-chloro-3-trifluoromethyl-1H-pyrazol-4-yl)-methanol

A solution of 39.9 g (156.9 mmoles) of(1-tert-butyl-5-chloro-3-trifluoromethyl-1H-pyrazole-4-carboaldehydedissolved in 300 ml of methanol was cooled to 0° C. Thereto wasgradually added 6.5 g (172.6 mmoles) of sodium borohydride. The mixturewas stirred at room temperature for 3 hours to give rise to a reaction.After the completion of the reaction, the reaction mixture was pouredinto water, followed by extraction with ethyl acetate. The resultingorganic layer was washed with an aqueous sodium chloride solution andthen dried over anhydrous magnesium sulfate. The resulting solution wassubjected to vacuum distillation to remove the solvent containedtherein, to obtain 37.7 g (yield: 93.6%) of(1-tert-butyl-5-chloro-3-trifluoromethyl-1H-pyrazol-4-yl)-methanol.

¹H-NMR [CDCl₃/TMS, δ (ppm)]:

4.60 (2H,d), 1.72 (9H,s), 1.58 (1H,t)

REFERENCE EXAMPLE 19 Production of4-bromomethyl-1-tert-butyl-5-chloro-3-trifluoromethyl-1H-pyrazole

A solution of 9.2 g (35.7 mmoles) of(1-tert-butyl-5-chloro-3-trifluoromethyl-1H-pyrazol-4-yl)-methanoldissolved in 100 ml of diethyl ether was cooled to −10° C. Thereto wasadded 11.6 g (42.9 mmoles) of phosphorus tribromide. The mixture wasstirred at room temperature overnight to give rise to a reaction. Afterthe completion of the reaction, the reaction mixture was poured intowater, followed by extraction with diethyl ether. The resulting organiclayer was washed with an aqueous sodium chloride solution and then driedover anhydrous magnesium sulfate. The resulting solution was subjectedto vacuum distillation to remove the solvent contained therein, toobtain 10.0 g (yield: 87.3%) of4-bromomethyl-1-tert-butyl-5-chloro-3-trifluoromethyl-1H-pyrazole.

REFERENCE EXAMPLE 20 Production of(1-tert-butyl-5-chloro-3-trifluoromethyl-1H-pyrazol-4-yl)-methanethiol

43.5 g (136.1 mmoles) of4-bromomethyl-1-tert-butyl-5-chloro-3-trifluoromethyl-1H-pyrazole wasadded to a solution of 21.8 g of sodium hydrosulfide hydrate (purity:70%, 272.2 mmoles) dissolved in 300 ml of N,N-dimethylformamide. Themixture was stirred at room temperature overnight to give rise to areaction. After the completion of the reaction, the reaction mixture waspoured into water, followed by extraction with diethyl ether. Theresulting organic layer was washed with an aqueous sodium chloridesolution and then dried over anhydrous magnesium sulfate. The resultingsolution was subjected to vacuum distillation to remove the solventcontained therein, to obtain 32.3 g (yield: 87.0%) of(1-tert-butyl-5-chloro-3-trifluoromethyl-1H-pyrazol-4-yl)-methanethiol.

¹H-NMR [CDCl₃/TMS, δ (ppm)]:

3.65 (2H,d), 1.90 (1H,t), 1.70 (9H,s)

REFERENCE EXAMPLE 21 Production of1-tert-butyl-5-methoxy-3-trifluoromethyl-1H-pyrazole

15.0 g (108.4 mmoles) of anhydrous potassium carbonate and 19.3 g (135.5mmoles) of methyl iodide were added, at room temperature, to a solutionof 18.8 g (90.3 mmoles) of1-tert-butyl-3-trifluoromethyl-1H-pyrazol-5-ol dissolved in 100 ml ofN,N-dimethylformamide. The mixture was stirred for 15 hours to give riseto a reaction. After the completion of the reaction, the reactionmixture was poured into water, followed by extraction with diethylether. The resulting organic layer was washed with water and an aqueoussodium chloride solution in this order and then dried over anhydrousmagnesium sulfate. The resulting solution was subjected to vacuumdistillation to remove the solvent contained therein, to obtain 20.0 g(yield: 99.8%) of 1-tert-butyl-5-methoxy-3-trifluoromethyl-1H-pyrazole.

REFERENCE EXAMPLE 22 Production of1-tert-butyl-4-chloromethyl-5-methoxy-3-trifluoromethyl-1H-pyrazole

5.4 g of paraformaldehyde (180.2 mmoles in terms of formaldehyde) and 20ml of concentrated hydrochloric acid were added to a solution of 20.0 g(90.1 mmoles) of 1-tert-butyl-5-methoxy-3-trifluoromethyl-1H-pyrazoledissolved in 90 ml of acetic acid. The mixture was stirred at 60° C. for30 minutes to give rise to a reaction. After the completion of thereaction, the reaction mixture was poured into water, followed byextraction with diisopropyl ether. The resulting organic layer waswashed with water and then dried over anhydrous magnesium sulfate. Theresulting solution was subjected to vacuum distillation to remove thesolvent contained therein, to obtain 21.7 g (yield: 89.0%) of1-tert-butyl-4-chloromethyl-5-methoxy-3-trifluoromethyl-1H-pyrazole.

REFERENCE EXAMPLE 23 Production of3-methoxy-1-methyl-5-trifluoromethyl-1H-pyrazole

10.0 g (72.3 mmoles) of anhydrous potassium carbonate and 12.8 g (90.3mmoles) of methyl iodide were added, at room temperature, to a solutionof 10.0 g (60.2 mmoles) of3-hydroxy-1-methyl-5-trifluoromethyl-1H-pyrazole dissolved in 50 ml ofN,N-dimethylformamide. The mixture was stirred for 15 hours to give riseto a reaction. After the completion of the reaction, the reactionmixture was poured into water, followed by extraction with diethylether. The resulting organic layer was washed with water and an aqueoussodium chloride solution in this order and then dried over anhydrousmagnesium sulfate. The resulting solution was subjected to vacuumdistillation to remove the solvent contained therein, to obtain 9.8 g(yield: 90.7%) of 3-methoxy-1-methyl-5-trifluoromethyl-1H-pyrazole.

REFERENCE EXAMPLE 24 Production of4-chloromethyl-3-methoxy-1-methyl-5-trifluoromethyl-1H-pyrazole

0.45 g of paraformaldehyde (15.0 mmoles in terms of formaldehyde) and 5ml of concentrated hydrochloric acid were added to a solution of 1.00 g(5.6 mmoles) of 3-methoxy-1-methyl-5-trifluoromethyl-1H-pyrazoledissolved in 25 ml of acetic acid. The mixture was stirred at 80° C. for2 hours to give rise to a reaction. After the completion of thereaction, the reaction mixture was poured into water and neutralizedwith potassium carbonate, followed by extraction with ethyl acetate. Theresulting organic layer was washed with water and then dried overanhydrous magnesium sulfate. The resulting solution was subjected tovacuum distillation to remove the solvent contained therein. The residuewas purified by silica gel column chromatography (developing solvent:hexane-ethyl acetate mixed solvent) to obtain 0.83 g (yield: 65.0%) of4-chloromethyl-3-methoxy-1-methyl-5-trifluoromethyl-1H-pyrazole.

REFERENCE EXAMPLE 25 Production of5-fluoro-1-methyl-3-trifluoromethyl-1H-pyrazole-4-carboaldehyde

42.0 g (711.9 mmoles) of potassium fluoride was added to a solution of60.4 g (282.7 mmoles) of5-chloro-1-methyl-3-trifluoromethyl-1H-pyrazole-4-carboaldehydedissolved in 700 ml of dimethyl sulfoxide. The mixture was stirred at120 to 140° C. for 5 hours to give rise to a reaction. Afterconfirmation of the completion of the reaction, the reaction mixture waspoured into water, followed by extraction with ethyl acetate. Theresulting organic layer was washed with water and an aqueous sodiumchloride solution and then dried over anhydrous magnesium sulfate. Theresulting solution was subjected to vacuum distillation to remove thesolvent contained therein. The residue was purified by silica gel columnchromatography (developing solvent: hexane-ethyl acetate mixed solvent)to obtain 36.8 g (yield: 66.0%) of5-fluoro-1-methyl-3-trifluoromethyl-1H-pyrazole-4-carboaldehyde.

REFERENCE EXAMPLE 26 Production of(5-fluoro-1-methyl-3-trifluoromethyl-1H-pyrazol-4-yl)-methanol

To a solution of 3.9 g (102.6 mmoles) of sodium borohydride dissolved in500 ml of methanol was added, with ice-cooling, a solution of 36.8 g(187.6 mmoles) of5-fluoro-1-methyl-3-trifluoromethyl-1H-pyrazole-4-carboaldehydedissolved in 200 ml of methanol. The resulting mixture was stirred at 0°C. for 30 minutes to give rise to a reaction. After confirmation of thecompletion of the reaction, the reaction mixture was poured into water,followed by extraction with ethyl acetate. The resulting organic layerwas washed with water and an aqueous sodium chloride solution and thendried over anhydrous magnesium sulfate. The resulting solution wassubjected to vacuum distillation to remove the solvent containedtherein, to obtain 35.4 g (yield: 95.4%) of(5-fluoro-1-methyl-3-trifluoromethyl-1H-pyrazol-4-yl)-methanol.

REFERENCE EXAMPLE 27 Production of4-bromomethyl-5-fluoro-1-methyl-3-trifluoromethyl-1H-pyrazole

A solution of 35.4 g (178.7 mmoles) of5-fluoro-1-methyl-3-trifluoromethyl-1H-pyrazole-4-methanol dissolved in500 ml of diethyl ether was cooled to −30° C. Thereto was added 54.0 g(199.5 mmoles) of phosphorus tribromide. The mixture was stirred at roomtemperature for 12 hours to give rise to a reaction. After confirmationof the completion of the reaction, the reaction mixture was poured intowater, followed by extraction with diethyl ether. The resulting organiclayer was washed with water and an aqueous sodium chloride solution andthen dried over anhydrous magnesium sulfate. The resulting solution wassubjected to vacuum distillation to remove the solvent containedtherein, to obtain 31.4 g (yield: 80.8%) of4-bromomethyl-5-fluoro-1-methyl-3-trifluoromethyl-1H-pyrazole.

REFERENCE EXAMPLE 28 Production of (ethoxycarbonyl)malondialdehyde

12.6 g of sodium hydride (purity: 60%, 525.0 mmoles) was washed withdiethyl ether by decantation several times and then made into a solutionin 500 ml of diethyl ether. Thereto were added, in a nitrogen current at0 to 10° C., 194 g (2.6 moles) of ethyl formate and 50 g (262.0 mmoles)of ethyl 3,3-diethoxy-propionate. The resulting mixture was stirred atroom temperature for 15 hours to give rise to a reaction. Afterconfirmation of the completion of the reaction, the reaction mixture waspoured into water, followed by washing with diethyl ether. The resultingaqueous layer was allowed to have a pH of 1 with hydrochloric acid,followed by extraction with dichloromethane. The resulting organic layerwas washed with an aqueous sodium chloride solution and then dried overanhydrous magnesium sulfate. The resulting solution was subjected tovacuum distillation to remove the solvent contained therein, to obtain37.6 g (yield: 100%) of crude (ethoxycarbonyl)malondialdehyde as a darkred oily substance.

¹H-NMR [CDCl₃/TMS, δ (ppm)]:

9.09 (2H,s), 5.26 (1H,s), 4.27 (2H,q), 1.28 (3H,t)

REFERENCE EXAMPLE 29 Production of ethyl 1H-pyrazole-4-carboxylate

6.2 g (193 mmoles) of hydrazine was added, with ice-cooling, to asolution of 27.6 g (192 mmoles) of (ethoxycarbonyl)malondialdehydedissolved in 150 ml of ethanol. The mixture was stirred at roomtemperature for 17 hours to give rise to a reaction. The reactionmixture was subjected to vacuum distillation to remove the ethanolcontained therein. The residue was purified by silica gel columnchromatography (developing solvent: dichloromethane-ethyl acetate mixedsolvent) to obtain 19.4 g (72.4%) of ethyl 1H-pyrazole-4-carboxylate asyellow crystals.

¹H-NMR [CDCl₃/TMS, δ (ppm)]:

8.08 (2H,s), 5.30 (1H,s), 4.31 (2H,q), 1.36 (3H,t)

REFERENCE EXAMPLE 30 Production of ethyl1-ethyl-1H-pyrazole-4-carboxylate

3.7 g (26.8 mmoles) of anhydrous potassium carbonate and 4.2 g (26.6mmoles) of ethyl iodide were added to a solution of 1.5 g (10.7 mmoles)of ethyl 1H-pyrazole-4-carboxylate dissolved in 50 ml ofN,N-dimethylformamide. The mixture was stirred at room temperature for20 hours to give rise to a reaction. After confirmation of thecompletion of the reaction, the reaction mixture was poured into water,followed by extraction with ethyl acetate. The resulting organic layerwas washed with water and an aqueous sodium chloride solution and thendried over anhydrous magnesium sulfate. The resulting solution wassubjected to vacuum distillation to remove the solvent containedtherein. The residue was purified by silica gel column chromatography(developing solvent: hexane-ethyl acetate mixed solvent) to obtain 1.6 g(yield: 88.9%) of ethyl 1-ethyl-1H-pyrazole-4-carboxylate as a yellowoily substance.

¹H-NMR [CDCl₃/TMS, δ (ppm)]:

7.90 (2H,s), 4.28 (2H,q), 4.18 (2H,q), 1.51 (3H,t), 1.35 (3H,t)

REFERENCE EXAMPLE 31 Production of ethyl3,5-dichloro-1-ethyl-1H-pyrazole-4-carboxylate

In a glass sealed tube were placed 1.6 g (9.5 mmoles) of ethyl1-ethyl-1H-pyrazole-4-carboxylate and 5.1 g (38.3 mmoles) ofN-chlorosuccinimide. There were allowed to react at 160° C. for 6 hours.After the completion of the reaction, the reaction mixture was cooled toroom temperature, washed with carbon tetrachloride and chloroform, andfiltered under vacuum. The resulting filtrate (organic layer) was washedwith water and an aqueous sodium chloride solution and then dried overanhydrous magnesium sulfate. The resulting solution was subjected tovacuum distillation to remove the solvent contained therein. The residuewas purified by silica gel column chromatography (developing solvent:hexane-ethyl acetate mixed solvent) to obtain 1.0 g (yield: 44.2%) ofethyl 3,5-dichloro-1-ethyl-1H-pyrazole-4-carboxylate as a yellow oilysubstance.

¹H-NMR [CDCl₃/TMS, δ (ppm)]:

4.36 (2H,q), 4.21 (2H,q), 1.44 (3H,t), 1.38 (3H,t)

REFERENCE EXAMPLE 32 Production of(3,5-dichloro-1-ethyl-1H-pyrazol-4-yl)methanol

A solution of 0.16 g (4.2 mmoles) of lithium aluminum hydride dissolvedin 70 ml of tetrahydrofuran was cooled to −50° C. Thereto was graduallyadded dropwise a solution of 1.0 g (4.2 mmoles) of ethyl3,5-dichloro-1-ethyl-1H-pyrazole-4-carboxylate dissolved in 30 ml oftetrahydrofuran. The mixture was stirred at −50° C. for 3 hours to giverise to a reaction. After confirmation of the completion of thereaction, ethyl acetate was added, followed by stirring for a while.Water was added, followed by stirring for a while. The resulting mixturewas filtered under vacuum. The filtrate was extracted with ethylacetate. The resulting organic layer was washed with water and anaqueous sodium chloride solution and then dried over anhydrous magnesiumsulfate. The resulting solution was subjected to vacuum distillation toremove the solvent contained therein, to obtain 0.82 g (yield: 100%) of(3,5-dichloro-1-ethyl-1H-pyrazol-4-yl)methanol as a brown oilysubstance.

¹H-NMR [CDCl₃/TMS, δ (ppm)]:

4.52 (2H,s), 4.16 (2H,q), 1.43 (3H,t)

REFERENCE EXAMPLE 33 Production of4-bromomethyl-3,5-dichloro-1-ethyl-1H-pyrazole

A solution of 0.82 g (4.2 mmoles) of(3,5-dichloro-1-ethyl-1H-pyrazol-4-yl)methanol dissolved in 50 ml ofdiethyl ether was cooled to −30° C. Thereto was added 1.3 g (4.8 mmoles)of phosphorus tribromide. The mixture was stirred at room temperaturefor 12 hours to give rise to a reaction. After confirmation of thecompletion of the reaction, the reaction mixture was poured into water,followed by extraction with ethyl acetate. The resulting organic layerwas washed with water and an aqueous sodium chloride solution and thendried over anhydrous magnesium sulfate. The resulting solution wassubjected to vacuum distillation to remove the solvent containedtherein, to obtain 0.9 g (yield: 81.8%) of4-bromomethyl-3,5-dichloro-1-ethyl-1H-pyrazole as a yellow oilysubstance.

¹H-NMR [CDCl₃/TMS, δ (ppm)]:

4.33 (2H,s), 4.13 (2H,q), 1.43 (3H,t)

REFERENCE EXAMPLE 34 Production of3-difluoromethyl-1-methyl-1H-pyrazol-5-ol

8.3 g (180.6 mmoles) of methylhydrazine and 5 ml of concentratedhydrochloric acid were added to a solution of 30.0 g (180.6 mmoles) ofethyl difluoroacetoacetate dissolved in 200 ml of ethanol. The mixturewas refluxed for 2 days with heating, to give rise to a reaction. Afterthe completion of the reaction, the reaction mixture was subjected tovacuum distillation to remove the most part of the solvent containedtherein. The residue was poured into water. The mixture was allowed tohave a pH of 4 using citric acid and extracted with ethyl acetate. Theresulting organic layer was washed with water and an aqueous sodiumchloride solution in this order and then dried over anhydrous magnesiumsulfate. The resulting solution was subjected to vacuum distillation toremove the solvent contained therein. The residue was purified by silicagel column chromatography (developing solvent: hexane-ethyl acetatemixed solvent) to obtain 8.9 g (yield: 33.3%) of3-difluoromethyl-1-methyl-1H-pyrazol-5-ol.

REFERENCE EXAMPLE 35 Production of5-chloro-3-difluoromethyl-1-methyl-1H-pyrazole-4-carboaldehyde

41.6 g (270.1 mmoles) of phosphorus oxychloride was added, withice-cooling, to 7.9 g (108.0 mmoles) of N,N-dimethylformamide. Theretowas added, at room temperature, 8.0 g (54.0 mmoles) of3-difluoromethyl-1-methyl-1H-pyrazol-5-ol. The mixture was refluxed for4 hours with heating, to give rise to a reaction. After the completionof the reaction, the reaction mixture was poured into water, followed byextraction with chloroform. The resulting organic layer was washed withwater, a 5% aqueous sodium hydroxide solution and water in this orderand then dried over anhydrous magnesium sulfate. The resulting solutionwas subjected to vacuum distillation to remove the solvent containedtherein. The residue was purified by silica gel column chromatography(developing solvent: hexane-ethyl acetate mixed solvent) to obtain 7.7 g(yield: 73.3%) of5-chloro-3-difluoromethyl-1-methyl-1H-pyrazole-4-carboaldehyde as whitecrystals.

¹H-NMR [CDCl₃/TMS, δ (ppm)]:

9.96 (1H,s), 6.90 (1H,t, J=53.6 Hz), 3.93 (3H,s)

REFERENCE EXAMPLE 36 Production of(5-chloro-3-difluoromethyl-1-methyl-1H-pyrazol-4-yl)-methanol

A solution of 7.2 g (37.0 mmoles) of5-chloro-3-difluoromethyl-1-methyl-1H-pyrazole-4-carboaldehyde dissolvedin 100 ml of methanol was cooled to 0° C. Thereto was gradually added2.1 g (55.5 mmoles) of sodium borohydride. The mixture was stirred atroom temperature for 3 hours to give rise to a reaction. After thecompletion of the reaction, the reaction mixture was poured into water,followed by extraction with ethyl acetate. The resulting organic layerwas washed with an aqueous sodium chloride solution and then dried overanhydrous magnesium sulfate. The resulting solution was subjected tovacuum distillation to remove the solvent contained therein, to obtain3.8 g (yield: 52.1%) of(5-chloro-3-difluoromethyl-1-methyl-1H-pyrazol-4-yl)-methanol.

¹H-NMR [CDCl₃/TMS, δ (ppm)]:

6.70 (1H,t, J=40.8 Hz), 4.63 (2H,s), 3.86 (3H,s), 1.79 (1H,br)

REFERENCE EXAMPLE 37 Production of4-bromomethyl-5-chloro-3-difluoromethyl-1-methyl-1H-pyrazole

A solution of 2.0 g (10.0 mmoles) of(5-chloro-3-difluoromethyl-1-methyl-1H-pyrazol-4-yl)-methanol dissolvedin 50 ml of diethyl ether was cooled to −10° C. Thereto was added 1.0 g(3.5 mmoles) of phosphorus tribromide. The mixture was stirred at roomtemperature overnight to give rise to a reaction. After the completionof the reaction, the reaction mixture was poured into ice water,followed by extraction with diethyl ether. The resulting organic layerwas washed with an aqueous sodium chloride solution and then dried overanhydrous magnesium sulfate. The resulting solution was subjected tovacuum distillation to remove the solvent contained therein, to obtain2.6 g (yield: 100.0%) of4-bromomethyl-5-chloro-3-difluoromethyl-1-methyl-1H-pyrazole.

REFERENCE EXAMPLE 38 Production of trifluoroacetaldehyde oxime etherate

24.1 g (347.0 mmoles) of hydroxylamine hydrochloride and 160 ml of waterwere added to a solution of 50.0 g (347.0 mmoles) oftrifluoroacetaldehyde hemiethyl acetal dissolved in 80 ml of methanol.Thereto was dropwise added, with ice-cooling, 80.0 g of a 50% aqueoussodium hydroxide solution (1.7 moles). After the completion of thedropwise addition, the resulting mixture was stirred at room temperaturefor 6 hours to give rise to a reaction. After the completion of thereaction, 10% hydrochloric acid was added for pH adjustment to 6. Theresulting mixture was extracted with diethyl ether. The extract wassubjected to vacuum distillation to remove the solvent containedtherein. The residue was subjected to distillation to obtain 24.7 g(yield: 38.0%) of trifluoroacetaldehyde oxime etherate.

REFERENCE EXAMPLE 39 Production of trifluoroacetohydroximoyl bromideetherate

A solution of 38.8 g (218.0 mmoles) of N-bromosuccinimide dissolved in125 ml of N,N-dimethylformamide was added, with ice-cooling, to asolution of 24.7 g (131.7 mmoles) of trifluoroacetaldehyde oximeetherate dissolved in 50 ml of N,N-dimethylformamide. The mixture wasstirred at room temperature for 3 hours to give rise to a reaction.After the completion of the reaction, the reaction mixture was pouredinto water, followed by extraction with diethyl ether. The resultingorganic layer was washed with an aqueous sodium chloride solution andthen dried over anhydrous magnesium sulfate. The resulting solution wassubjected to vacuum distillation to remove the solvent containedtherein. The residue was subjected to distillation to obtain 33.3 g(yield: 95.0%) of trifluoroacetohydroximoyl bromide etherate as a brownoily substance.

¹H-NMR [CDCl₃/TMS, δ (ppm)]:

9.30 (1H,s)

REFERENCE EXAMPLE 40 Production of4-ethoxycarbonyl-5-methyl-3-trifluoromethylisoxazole

2.8 g (51.3 mmoles) of sodium methoxide was added to a solution of 6.7 g(51.3 mmoles) of ethyl acetoacetate dissolved in 80 ml of methanol.Thereto was added, with ice-cooling, a solution of 5.0 g (18.8 mmoles)of trifluorohydroximoyl bromide etherate dissolved in 20 ml of methanol.The resulting mixture was stirred at room temperature for 3 hours togive rise to a reaction. After the completion of the reaction, thereaction mixture was subjected to vacuum distillation to remove thesolvent contained therein. Water was added to the residue, followed byextraction with chloroform. The resulting organic layer was washed withan aqueous sodium chloride solution and then dried over anhydrousmagnesium sulfate. The resulting solution was subjected to vacuumdistillation to remove the solvent contained therein. The residue waspurified by silica gel column chromatography (developing solvent:hexane-ethyl acetate mixed solvent) to obtain 2.9 g (yield: 69.0%) of4-ethoxycarbonyl-5-methyl-3-trifluoromethylisoxazole as a colorless oilysubstance.

¹H-NMR [CDCl₃/TMS, δ (ppm)]:

4.36 (2H,q), 2.77 (3H,s), 1.37 (3H,t)

REFERENCE EXAMPLE 41 Production of(5-methyl-3-trifluoromethylisoxazol-4-yl)-methanol

A solution of 0.16 g (4.2 mmoles) of lithium aluminum hydride dissolvedin 15 ml of THF was cooled to 0° C. Thereto was gradually added asolution of 0.93 g (4.2 mmoles) of4-ethoxycarbonyl-5-methyl-3-trifluoromethylisoxazole dissolved in 15 mlof THF. The mixture was stirred at 0° C. for 1 hour to give rise to areaction. After the completion of the reaction, ethyl acetate was added,followed by stirring for a while. Water was added, followed by stirringfor a while. The reaction mixture was filtered under vacuum. Thefiltrate was extracted with diethyl ether. The resulting organic layerwas washed with an aqueous sodium chloride solution and then dried overanhydrous magnesium sulfate. The resulting solution was subjected tovacuum distillation to remove the solvent contained therein, to obtain0.5 g (yield: 60.0%) of(5-methyl-3-trifluoromethylisoxazol-4-yl)-methanol.

¹H-NMR [CDCl₃/TMS, δ (ppm)]:

4.60 (2H,d), 2.54 (3H,s), 1.66 (1H, br)

REFERENCE EXAMPLE 42 Production of4-bromomethyl-5-methyl-3-trifluoromethylisoxazole

A solution of 0.45 g (2.5 mmoles) of(5-methyl-3-trifluoromethylisoxazol-4-yl)-methanol dissolved in 10 ml ofdiethyl ether was cooed to 0° C. Thereto was added 0.2 g (8.9 mmoles) ofphosphorus tribromide. The mixture was stirred at room temperature for 1hour to give rise to a reaction. After the completion of the reaction,the reaction mixture was poured into water, followed by extraction withdiethyl ether. The resulting organic layer was washed with an aqueoussodium chloride solution and then dried over anhydrous magnesiumsulfate. The resulting solution was subjected to vacuum distillation toremove the solvent contained therein, to obtain 0.5 g (yield: 74.0%) of4-bromomethyl-5-methyl-3-trifluoromethylisoxazole.

¹H-NMR [CDCl₃/TMS, δ (ppm)]:

4.31 (2H,d), 2.51 (3H,s)

REFERENCE EXAMPLE 43 Production of(5-chloro-3-methyl-isothiazol-4-yl)-methanol

A solution of 2.06 g (10.0 mmoles) of ethyl5-chloro-3-methyl-isothiazole-4-carboxylate dissolved in 10 ml of THFwas dropwise added, at −30° C., to a solution of 0.42 g (11.0 mmoles) oflithium aluminum hydride dissolved in 10 ml of THF. The mixture wasstirred at the same temperature for 1 hour to give rise to a reaction.After confirmation of the completion of the reaction, ethyl acetate wasadded to the reaction mixture. The resulting mixture was poured intowater, followed by extraction with ethyl acetate. The resulting organiclayer was washed with water and an aqueous sodium chloride solution inthis order and then dried over anhydrous magnesium sulfate. Theresulting solution was subjected to vacuum distillation to remove thesolvent contained therein. The residue was purified by silica gel columnchromatography to obtain 1.50 g (yield: 91.5%) of(5-chloro-3-methyl-isothiazol-4-yl)-methanol.

REFERENCE EXAMPLE 44 Production of4-chloromethyl-5-chloro-3-methylisothiazole

3.26 g (27.44 mmoles) of thionyl chloride was added, at roomtemperature, to a solution of 1.50 g (9.15 mmoles) of(5-chloro-3-methyl-isothiazol-4-yl)-methanol dissolved in 10 ml ofchloroform. The mixture was stirred for 3 hours to give rise to areaction. After confirmation of the completion of the reaction, thereaction mixture was subjected to vacuum distillation to remove thesolvent contained therein, to obtain 1.67 g (yield: quantitative) of4-chloromethyl-5-chloro-3-methylisothiazole.

REFERENCE EXAMPLE 45 Production of methyl 4-trifluoromethylnicotinate

6.7 g (48.6 mmoles) of anhydrous potassium carbonate and 6.9 g (48.6mmoles) of methyl iodide were added to a solution of 4.6 g (24.1 mmoles)of 4-trifluoromethylnicotinic acid dissolved in 70 ml ofN,N-dimethylformamide. The mixture was stirred at room temperature for12 hours to give rise to a reaction. After confirmation of thecompletion of the reaction, the reaction mixture was poured into water,followed by extraction with ethyl acetate. The resulting organic layerwas washed with water and an aqueous sodium chloride solution and thendried over anhydrous magnesium sulfate. The resulting solution wassubjected to vacuum distillation to remove the solvent containedtherein. The residue was purified by silica gel column chromatography(developing solvent: hexane-ethyl acetate mixed solvent) to obtain 2.77g (yield: 56.1%) of methyl 4-trifluoromethylnicotinate as a yellow oilysubstance.

¹H-NMR [CDCl₃/TMS, δ (ppm)]:

9.11 (1H,s), 8.92 (1H,d), 7.64 (1H,d), 3.99 (3H,s)

REFERENCE EXAMPLE 46 Production of(4-trifluoromethylpyridin-3-yl)-methanol

A solution of 0.37 g (9.7 mmoles) of lithium aluminum hydride dissolvedin 100 ml of THF was cooled to −50° C. Thereto was gradually addeddropwise a solution of 2.0 g (9.8 mmoles) of methyl4-trifluoromethylnicotinate dissolved in 30 ml of THF. The mixture wasstirred at −50° C. for 3 hours to give rise to a reaction. Afterconfirmation of the completion of the reaction, ethyl acetate was added,followed by stirring for a while. Water was added, followed by stirringfor a while. The reaction mixture was filtered under vacuum. Thefiltrate was extracted with ethyl acetate. The resulting organic layerwas washed with water and an aqueous sodium chloride solution and thendried over anhydrous magnesium sulfate. The resulting solution wassubjected to vacuum distillation to remove the solvent containedtherein. The residue was purified by silica gel column chromatography(developing solvent: hexane-ethyl acetate mixed solvent) to obtain 0.6 g(yield: 35.3%) of (4-trifluoromethylpyridin-3-yl)-methanol as a yellowoily substance.

¹H-NMR [CDCl₃/TMS, δ (ppm)]:

9.00 (1H,s), 8.73 (1H,d), 7.51 (1H,d), 4.95 (2H,s)

REFERENCE EXAMPLE 47 Production of3-bromomethyl-4-trifluoromethylpyridine

A solution of 0.6 g (3.4 mmoles) of(4-trifluoromethylpyridin-3-yl)-methanol dissolved in 50 ml of diethylether was cooed to −30° C. Thereto was added 1.4 g (5.2 mmoles) ofphosphorus tribromide. The mixture was stirred at room temperature for12 hours to give rise to a reaction. After confirmation of thecompletion of the reaction, the reaction mixture was poured into water,followed by extraction with ethyl acetate. The resulting organic layerwas washed with water and an aqueous sodium chloride solution and thendried over anhydrous magnesium sulfate. The resulting solution wassubjected to vacuum distillation to remove the solvent containedtherein, to obtain 0.61 g (yield: 75.3%) of3-bromomethyl-4-trifluoromethylpyridine as a yellow oily substance.

¹H-NMR [CDCl₃/TMS, δ (ppm)]:

8.88 (1H,s), 8.73 (1H,d), 7.54 (1H,d), 4.63 (2H,s)

REFERENCE EXAMPLE 48 Production of5-bromo-4-hydroxy-6-trifluoromethylpyrimidine

77.5 g (945.0 mmoles) of anhydrous sodium acetate was added, at roomtemperature, to a solution of 49.2 g (300.0 mmoles) of4-hydroxy-6-trifluoromethylpyrimidine dissolved in 600 ml of aceticacid. Thereto was gradually added 50.3 g (315 mmoles) of bromine at 45°C. The resulting mixture was stirred at the same temperature for 3 hoursto give rise to a reaction. After confirmation of the completion of thereaction, the reaction mixture was subjected to vacuum distillation toremove the solvent contained therein. The residue was poured into water,followed by extraction with ethyl acetate. The resulting organic layerwas washed with water and an aqueous sodium chloride solution in thisorder and then dried over anhydrous magnesium sulfate. The resultingsolution was subjected to vacuum distillation to remove the solventcontained therein. The residue was washed with n-hexane to obtain 38.9 g(yield: 53.4%) of 5-bromo-4-hydroxy-6-trifluoromethylpyrimidine.

REFERENCE EXAMPLE 49 Production of5-bromo-4-chloro-6-trifluoromethylpyrimidine

24.3 g (100.0 mmoles) of 5-bromo-4-hydroxy-6-trifluoromethylpyrimidinewas suspended in 18.5 g (120.0 mmoles) of phosphorus oxychloride. Themixture was stirred at 100° C. for 2 hours to give rise to a reaction.After confirmation of the completion of the reaction, the reactionmixture was poured into water gradually, followed by extraction withchloroform. The resulting organic layer was washed with water and anaqueous sodium chloride solution in this order and then dried overanhydrous magnesium sulfate. The resulting solution was subjected tovacuum distillation to remove the solvent contained therein. The residuewas purified by silica gel column chromatography to obtain 21.5 g(yield: 82.4%) of 5-bromo-4-chloro-6-trifluoromethylpyrimidine.

REFERENCE EXAMPLE 50 Production of5-bromo-4-methoxy-6-trifluoromethylpyrimidine

16.7 ml of sodium methoxide (a 28% methanol solution, 86.4 mmoles) wasadded, at room temperature, to a solution of 21.5 g (82.2 mmoles) of5-bromo-4-chloro-6-trifluoromethylpyrimidine dissolved in 100 ml ofmethanol. The mixture was stirred to give rise to a reaction. Afterconfirmation of the completion of the reaction, the reaction mixture wassubjected to vacuum distillation to remove the solvent containedtherein. The residue was poured into water, followed by extraction withchloroform. The resulting organic layer was washed with water and anaqueous sodium chloride solution in this order and then dried overanhydrous magnesium sulfate. The resulting solution was subjected tovacuum distillation to remove the solvent contained therein. The residuewas washed with n-hexane to obtain 19.2 g (yield: 91.0%) of5-bromo-4-methoxy-6-trifluoromethylpyrimidine.

REFERENCE EXAMPLE 51 Production of5-bromo-4-ethoxy-6-trifluoromethylpyrimidine

0.94 g (13.77 mmoles) of sodium ethoxide was added, at room temperature,to a solution of 3.00 g (11.48 mmoles) of5-bromo-4-chloro-6-trifluoromethylpyrimidine dissolved in 50 ml ofethanol. The mixture was stirred to give rise to a reaction. Afterconfirmation of the completion of the reaction, the reaction mixture wassubjected to vacuum distillation to remove the solvent containedtherein. The residue was poured into water, followed by extraction withchloroform. The resulting organic layer was washed with water and anaqueous sodium chloride solution in this order and then dried overanhydrous magnesium sulfate. The resulting solution was subjected tovacuum distillation to remove the solvent contained therein. The residuewas purified by silica gel column chromatography to obtain 2.44 g(yield: 82.9%) of 5-bromo-4-ethoxy-6-trifluoromethylpyrimidine.

REFERENCE EXAMPLE 52 Production of4-methoxy-6-trifluoromethylpyrimidine-5-carboaldehyde

30.0 ml of n-butyllithium (a 1.6 moles/liter n-hexane solution, 48.0mmoles) was gradually added, at −65 to −60° C., to a solution of 10.3 g(40.0 mmoles) of 5-bromo-4-methoxy-6-trifluoromethylpyrimidine dissolvedin 100 ml of tetrahydrofuran. The mixture was stirred for 30 minutes.Thereto was added 3.6 g (48.0 mmoles) of ethyl formate at the sametemperature. The resulting mixture was stirred at the same temperaturefor 3 hours to give rise to a reaction. The reaction mixture was pouredinto water, followed by extraction with ethyl acetate. The resultingorganic layer was washed with water and an aqueous sodium chloridesolution in this order and then dried over anhydrous magnesium sulfate.The resulting solution was subjected to vacuum distillation to removethe solvent contained therein. The residue was purified by silica gelcolumn chromatography to obtain 1.3 g (yield: 15.8%) of4-methoxy-6-trifluoromethylpyrimidine-5-carboaldehyde.

¹H-NMR [CDCl₃/TMS, δ (ppm)]:

10.41 (1H,q), 8.91 (1H,s), 4.18 (3H,s)

REFERENCE EXAMPLE 53 Production of4-ethoxy-6-trifluoromethylpyrimidine-5-carboaldehyde

A solution of 5.76 g (21.3 mmoles) of5-bromo-4-ethoxy-6-trifluoromethylpyrimidine dissolved in 250 ml of THFwas cooled to −78° C. Thereto was dropwise added 22.6 ml ofn-butyllithium (a 1.6 moles/liter n-hexane solution, 36.1 mmoles). Themixture was stirred for 40 minutes. Thereto was added 2.7 g (45.1mmoles) of methyl formate. The resulting mixture was stirred for 1.5hours to give rise to a reaction. After the completion of the reaction,an aqueous ammonium chloride solution was added. The mixture wasextracted with diethyl ether. The resulting organic layer was washedwith an aqueous sodium chloride solution and then dried over anhydrousmagnesium sulfate. The resulting solution was subjected to vacuumdistillation to remove the solvent contained therein. The residue waspurified by silica gel column chromatography (developing solvent:hexane-ethyl acetate mixed solvent) to obtain 3.82 g (yield: 81.6%) of4-ethoxy-6-trifluoromethylpyrimidine-5-carboaldehyde.

¹H-NMR (CDCl₃/TMS, δ (ppm)]:

10.41 (1H,s), 8.95 (1H,s), 4.63 (2H,q), 1.48 (3H,t)

REFERENCE EXAMPLE 54 Production of(4-methoxy-6-trifluoromethylpyrimidin-5-yl)-methanol

0.24 g (6.3 mmoles) of sodium borohydride was gradually added, at roomtemperature, to a solution of 1.3 g (6.3 mmoles) of4-methoxy-6-trifluoromethylpyrimidine-5-carboaldehyde dissolved in 30 mlof methanol. The mixture was stirred for 3 hours to give rise to areaction. After confirmation of the completion of the reaction, thereaction mixture was poured into water, followed by extraction withethyl acetate. The resulting organic layer was washed with water and anaqueous sodium chloride solution in this order and then dried overanhydrous magnesium sulfate. The resulting solution was subjected tovacuum distillation to remove the solvent contained therein. The residuewas purified by silica gel column chromatography to obtain 0.42 g(yield: 32.1%) of (4-methoxy-6-trifluoromethylpyrimidin-5-yl)-methanol¹H-NMR [CDCl₃/TMS, δ (ppm)]:

8.93 (1H,s), 4.81 (2H,s), 4.13 (3H,s), 2.26 (1H,br)

REFERENCE EXAMPLE 55 Production of(4-ethoxy-6-trifluoromethylpyrimidin-5-yl)-methanol

A solution of 3.82 g (17.2 mmoles) of4-ethoxy-6-trifluoromethylpyrimidine-5-carboaldehyde dissolved in 50 mlof methanol was added, with ice-cooling, to a solution of 1.7 g (45.7mmoles) of sodium borohydride dissolved in 50 ml of methanol. Themixture was stirred at 0° C. for 1 hour to give rise to a reaction.After the completion of the reaction, the reaction mixture was pouredinto water, followed by extraction with ethyl acetate. The resultingorganic layer was washed with an aqueous sodium chloride solution andthen dried over anhydrous magnesium sulfate. The resulting solution wassubjected to vacuum distillation to remove the solvent containedtherein, to obtain 3.77 g (yield: 97.8%) of(4-ethoxy-6-trifluoromethylpyrimidin-5-yl)-methanol

¹H-NMR [CDCl₃/TMS, δ (ppm)]:

8.80 (1H,s), 4.81 (2H,s), 4.59 (2H,q), 2.28 (1H,b), 1.48 (3H,t)

REFERENCE EXAMPLE 56 Production of5-chloromethyl-4-methoxy-6-trifluoromethylpyrimidine

1.19 g (10.1 mmoles) of thionyl chloride was added, at room temperature,to a solution of 0.42 g (2.02 mmoles) of(4-methoxy-6-trifluoromethylpyrimidin-5-yl)-methanol. The mixture wasstirred for 3 hours to give rise to a reaction. After confirmation ofthe completion of the reaction, the reaction mixture was subjected tovacuum distillation to remove the solvent contained therein, to obtain0.45 g (yield: quantitative) of5-chloromethyl-4-methoxy-6-trifluoromethylpyrimidine.

REFERENCE EXAMPLE 57 Production of5-bromomethyl-4-ethoxy-6-trifluoromethylpyrimidine

A solution of 3.77 g (17.0 mmoles) of(4-ethoxy-6-trifluoromethylpyrimidin-5-yl)-methanol dissolved in 50 mlof diethyl ether was cooled to 0° C. Thereto was added 2.0 g (7.2mmoles) of phosphorus tribromide. The mixture was stirred at roomtemperature for 1 hour. The resulting salt was dissolved using methanol.The resulting mixture was stirred for 1 hour to give rise to a reaction.The reaction mixture was poured into water, followed by extraction withdiethyl ether. The resulting organic layer was washed with an aqueoussodium chloride solution and then dried over anhydrous magnesiumsulfate. The resulting solution was subjected to vacuum distillation toremove the solvent contained therein, to obtain crude5-bromomethyl-4-ethoxy-6-trifluoromethylpyrimidine.

¹H-NMR [CDCl₃/TMS, δ (ppm)]:

8.79 (1H,s), 4.61 (2H,q), 4.55 (2H,s), 1.49 (3H,t)

REFERENCE EXAMPLE 58 Production of4-methoxy-6-trifluoromethylpyrimidine-5-carboaldehyde

30.0 ml (48.0 mmol) of n-butyllithium (1.6 mol/l n-hexane solution) wasslowly added to 100 ml of tetrahydrofuran solution containing 10.3 g(40.0 mmol) of 5-bromo-4-methoxy-6-trifluoromethylpyrimidine at −65 to−60° C., and the resultant mixture was stirred at 30 minutes. Further,3.6 g (48.0 mmol) of ethyl formate was added thereto at the sametemperature, and the mixture was stirred for 3 hours at the sametemperature. The resultant reaction solution was poured into water andwas extracted with ethyl acetate. The organic phase thus obtained waswashed with water and an aqueous sodium chloride solution in this order,and then dried over anhydrous magnesium sulfate. The resultant solutionwas subjected to vacuum distillation to remove the solvent containedtherein. The residue was purified by silica gel column chromatography toobtain 1.3 g (yield: 15.8%) of4-methoxy-6-trifluoromethylpyrimidine-5-carboaldehyde.

¹H-NMR [CDCl₃/TMS δ (ppm)] 10.41(1H,q) 8.98(1H,s), 4.18(3H,s)

REFERENCE EXAMPLE 59 Production of(2-chloro-4-methylpyridin-3-yl)methanol

A solution of 1.9 g (10.0 mmoles) of methyl 2-chloro-4-methylnicotinatedissolved in 5.0 ml of THF was gradually added, at −65 to −60° C., to asuspension of 0.4 g (10.0 mmoles) of lithium aluminum hydride in 30 mlof tetrahydrofuran. The mixture was stirred for 30 minutes and at −20°C. for 1 hour to give rise to a reaction. The reaction mixture waspoured into water, followed by extraction with ethyl acetate. Theresulting organic layer was washed with water and an aqueous sodiumchloride solution in this order and then dried over anhydrous magnesiumsulfate. The resulting solution was subjected to vacuum distillation toremove the solvent contained therein. The residue was purified by silicagel column chromatography to obtain 0.6 g (yield: 38.2%) of(2-chloro-4-methylpyridin-3-yl)methanol.

¹H-NMR [CDCl₃/TMS, δ (ppm)]:

8.19 (1H,d), 7.08 (1H,d), 4.85 (2H,s), 2.49 (3H,s)

REFERENCE EXAMPLE 60 Production of3-acetyl-4-chloromethyl-2,5-dichlorothiophene

33 ml of titanium tetrachloride (a 2 moles/liter dichloromethanesolution, 66.0 mmoles) was dropwise added, at 10° C. with ice-cooling,to a solution of 5.0 g (32.4 mmoles) of 3-acetyl-2,5-dichlorothiophenedissolved in 26 ml (323.0 mmoles) of chloromethyl methyl ether. Themixture was stirred at room temperature for 2 hours to give rise to areaction. After the completion of the reaction, the reaction mixture waspoured into ice water, followed by extraction with chloroform. Theresulting organic layer was washed with sodium bicarbonate, water and anaqueous sodium chloride solution in this order and then dried overanhydrous magnesium sulfate. The resulting solution was subjected tovacuum distillation to remove the solvent contained therein. The residuewas purified by silica gel column chromatography (developing solvent:hexane/ethyl acetate=9/1) to obtain 2.6 g (yield: 39.7%) of3-acetyl-4-chloromethyl-2,5-dichlorothiophene as yellow crystals.

¹H-NMR [CDCl₃/TMS, δ (ppm)]:

4.70 (2H,s), 2.56 (3H,s), 2.54 (3H,s), 2.39 (3H,s)

REFERENCE EXAMPLE 61 Production of 3-bromo-2-bromomethylbenzofuran

2.7 g (15.3 mmoles) of N-bromosuccinimide and 0.4 g (2.7 mmoles) ofazobisisobutyronitrile were added to a solution of 2.8 g (13.3 mmoles)of 3-bromo-2-methylbenzofuran dissolved in 30 ml of monochlorobenzene.The mixture was stirred at 80° C. for 30 minutes to give rise to areaction. After confirmation of the disappearance of the raw materials,the reaction mixture was cooled to room temperature. The insolubles wereremoved by filtration. The filtrate was subjected to vacuum distillationto remove the solvent contained therein. The residue was poured intowater, followed by extraction with ethyl acetate. The resulting organiclayer was washed with water and an aqueous sodium chloride solution inthis order and then dried over anhydrous magnesium sulfate. Theresulting solution was subjected to vacuum distillation to remove thesolvent contained therein, to obtain 3.0 g (yield: 79.0%) of3-bromo-2-bromomethylbenzofuran.

REFERENCE EXAMPLE 62 Production of ethyl1-difluoromethyl-1H-pyrazole-4-carboxylate

6.0 g (43.5 mmoles) of anhydrous potassium carbonate was added to asolution of 3.0 g (21.4 mmoles) of ethyl 1H-pyrazole-4-carboxylatedissolved in 100 ml of N,N-dimethylformamide. Thereinto was blownchlorodifluoromethane. The resulting mixture was stirred at 130 to 140°C. for 3 hours to give rise to a reaction. After confirmation of thecompletion of the reaction, the reaction mixture was poured into water,followed by extraction with ethyl acetate. The resulting organic layerwas washed with water and an aqueous sodium chloride solution and thendried over anhydrous magnesium sulfate. The resulting solution wassubjected to vacuum distillation to remove the solvent containedtherein. The residue was purified by silica gel column chromatography(developing solvent: hexane-ethyl acetate mixed solvent) to obtain 1.67g (yield: 41.0%) of ethyl 1-difluoromethyl-1H-pyrazole-4-carboxylate asa colorless transparent oily substance.

¹H-NMR [CDCl₃/TMS, δ (ppm)]:

8.32 (1H,s), 8.04 (1H,s), 7.20 (1H,t), 4.32 (2H,q), 1.37 (3H,t)

Now, Working Examples are illustrated below. In the Examples, “part”means “part by weight”.

<Formulation 1> Wettable Powder

5 Parts of compound No. 3-0002 and 40 parts of cyanazine were mixed with0.5 part of polyoxyethylene octylphenyl ether, 0.5 part of a sodium saltof an alkaylnaphthalenesulfonic acid-formalin condensate, 12 parts ofdiatomaceous earth and 42 parts of clay. The mixture was mixed andpulverized to obtain a wettable powder.

The amount of the herbicidal composition of the present invention variesdepending on a mixing ratio, weather conditions, a form of formulation,an application time, an application method, an application place, atarget weed, a target crop or the like, but is usually from 50 to 1500 gper hectare as a total amount of active ingredients. In a case of anemulsion, a wettable powder, a suspension or the like, a predeterminedamount is diluted with water in an amount of from 100 to 1000 liters perhectare to be applied.

The effect of the herbicidal composition of the present invention isillustrated by the following Application Examples.

APPLICATION EXAMPLE 1 Test for Herbicidal Effect by Upland Field SoilTreatment

An upland field soil was filled in a plastic pot of 11 cm each oflength, width and depth. Seeds of corn, green foxtail (Setaria viridis)and common lambsquarters (Chenopodium album L.) were sowed, followed bycovering with the same soil. The wettable powder produced in accordancewith Formulation 1 was weighed so as to provide active ingredients in apredetermined amount, and was diluted with water and sprayed uniformlyon the soil surface using a small sprayer, in an amount of 100 litersper 10 ares. Then, growing was made in a greenhouse, and the herbicidaleffect of each wettable powder was examined at the 30th day from thetreatment in accordance with the standard shown in Table 15. The resultsare shown in Tables 16 and 17. TABLE 15 Herbicidal effect (extent ofgrowth inhibition) or Index phytotoxicity 10 Herbicidal effect of growthinhibition or phytotoxicity of 100% 9 Herbicidal effect or phytotoxicityof from 90 to 99% 8 Herbicidal effect or phytotoxicity of from 80 to 89%7 Herbicidal effect or phytotoxicity of from 70 to 79% 6 Herbicidaleffect or phytotoxicity of from 60 to 69% 5 Herbicidal effect orphytotoxicity of from 50 to 59% 4 Herbicidal effect or phytotoxicity offrom 40 to 49% 3 Herbicidal effect or phytotoxicity of from 30 to 39% 2Herbicidal effect or phytotoxicity of from 20 to 29% 1 Herbicidal effector phytotoxicity of from 10 to 19% 0 Herbicidal effect or phytotoxicityof from 0 to 9%

TABLE 16 Herbicidal effect Amounts of Common active Green foxtaillambsquarter ingredient (Sataria (Chenopodium Compound (g a.i./ha) Cornviridis) album L.) 3-0002 32 0 5 2 Cyanazine 500 0 1 2 3-0002 +Cyanazine 32 + 500 0 10 7 3-0004 32 0 3 2 Cyanazine 500 0 1 2 3-0004 +Cyanazine 32 + 500 0 9 7 3-0005 32 0 2 2 Cyanazine 500 0 1 2 3-0005 +Cyanazine 32 + 500 0 9 6 3-0010 16 0 2 2 Cyanazine 500 0 1 2 3-0010 +Cyanazine 16 + 500 0 10 8 3-0011 16 0 3 2 Cyanazine 500 0 1 2 3-0011 +Cyanazine 16 + 500 0 10 8 3-0012 16 0 2 1 Cyanazine 500 0 1 2 3-0012 +Cyanazine 16 + 500 0 9 7 3-0013 16 0 2 2 Cyanazine 500 0 1 2 3-0013 +Cyanazine 16 + 500 0 9 7 3-0014 32 0 2 2 Cyanazine 500 0 1 2 3-0014 +Cyanazine 32 + 500 0 9 8 3-0015 32 0 3 3 Cyanazine 500 0 1 2 3-0015 +Cyanazine 32 + 500 0 9 8 3-0016 16 0 3 3 Cyanazine 500 0 1 2 3-0016 +Cyanazine 16 + 500 0 10 9 3-0017 16 0 3 3 Cyanazine 500 0 1 2 3-0017 +Cyanazine 16 + 500 0 9 9 3-0018 16 0 3 3 Cyanazine 500 0 1 2 3-0018 +Cyanazine 16 + 500 0 10 9 4-0001 32 0 2 1 Cyanazine 500 0 1 2 4-0001 +Cyanazine 32 + 500 0 8 7

TABLE 17 Herbicidal effect Amounts of Common active Green foxtaillambsquarter ingredient (Sataria (Chenopodium Compound (g a.i./ha) Cornviridis) album L.) 4-0002 32 0 3 2 Cyanazine 500 0 1 2 4-0002 +Cyanazine 32 + 500 0 9 7 2-0001 32 0 2 1 Cyanazine 500 0 1 2 2-0001 +Cyanazine 32 + 500 0 8 7 8-0001 16 0 2 1 Cyanazine 500 0 1 2 8-0001 +Cyanazine 16 + 500 0 9 7 3-0039 16 0 3 3 Cyanazine 500 0 1 2 3-0039 +Cyanazine 16 + 500 0 10 9 3-0188 16 0 3 2 Cyanazine 500 0 1 2 3-0188 +Cyanazine 16 + 500 0 10 9 3-0190 16 0 3 1 Cyanazine 500 0 1 2 3-0190 +Cyanazine 16 + 500 0 10 9

APPLICATION EXAMPLE 2 Test for Herbicidal Effect by Upland Field SoilTreatment

An upland field soil was filled in a plastic pot of 11 cm each oflength, width and depth. Seeds of corn and velvetleaf (Abutilontheophrasti Medic) were sowed, followed by covering with the same soil.The wettable powder produced in accordance with Formulation 1 wasweighed so as to provide active ingredients in a predetermined amount,and was diluted with water and sprayed uniformly on the soil surfaceusing a small sprayer, in an amount of 100 liters per 10 ares. Then,growing was made in a greenhouse, and the herbicidal effect of eachwettable powder was examined at the 30th day from the treatment inaccordance with the standard shown in Table 15. The results are shown inTable 18. TABLE 18 Amounts of Velvetleaf active (Abutilon ingredienttheophrasti Compound (g a.i./ha) Corn Medic) Compound 3-188 16 0 2Compound 3-188 32 0 2 Atrazine 125 0 1 Compound-3188 16-125 0 7 AtrazineCompund 3-188 32-125 0 10 Atrazine

INDUSTRIAL APPLICABILITY

The herbicidal composition of the present invention, which comprises acompound of the formula (I) and at least one compound selected fromGroup A, achieves not a simple total herbicidal activity but asynergistic herbicidal effect. Thus, the composition of the presentinvention achieves an excellent herbicidal effect at a small dose tovarious weeds growing on an upland field in a wide term range of frombefore germination to growing season, such as gramineous weeds includingbarnyardgrass (Echinochloa crusglli var. crus-galli), crabgrass(Digitaria ciliaris), green foxtail (Setaria viridis), annual bluegrass(Poa annua), johnsongrass (Sorghum halepense Pers.), blackgrass(Alopecurus myosuroides), wild oats (Avena fatua), and the like, broadleaf weeds including pale persicaria (Polygonum lapathifolia), slenderamaranth (Amaranthus viridis), common lambsquarters (Chenopodium albumL.), common chickweed (Stellaria media Villars), velvetleaf (Abutilontheophrasti Medic), prickly sida (Sida spinosa L.), Hemp sesbania(Sesbania exaltata Cory), common ragweed (Ambrosia artemisiifolia),morningglory, and the like, and annual and perennial sedge weedsincluding purple nutsedge (Cyperus rotundus L.), yellow nutsedge(Cyperus esculentus L.), hime-kugu (Cyperus brevifolius H.), sedge weed(Cyperus microiria Steud), rice flatsedge (Cyperus iria L.), and thelike.

Further, the composition of the present invention achieves an excellentherbicidal effect at a small dose to various weeds growing on a paddyfield in a wide term range of from before germination to growing season,such as annual weeds including watergrass (Echinochloa oryzicola),smallflower umbrella plant (Cyperus difformis), konagi (Monochoriavaginalis), aze-na (Lindernia procumbens), and the like and perennialweeds including mizu-gayatsuri (Cyperus serotinus), kuroguwai(Eleocharis kuroguwai), inu-hotaru-i (Scirpus juncoides), and the like.

On the other hand, the herbicidal composition of the present inventionis safe to aimed crop, particularly safe to rice, wheat, barley, corn,grain sorghum, soybeans, cotton, sugar beet, turf, fruit trees, and thelike.

1. A herbicidal composition which comprises i) an isoxazoline derivativerepresented by the following formula (I) or a salt thereof

wherein R¹ and R² are independently a hydrogen atom, a C1 to C10 alkylgroup, a C3 to C8 cycloalkyl group or a C3 to C8 cycloalkyl C1 to C3alkyl group; or R¹ and R² may be bonded to each other to form a C3 to C7spiro ring together with the carbon atoms to which they bond; R³ and R⁴are independently a hydrogen atom, a C1 to C10 alkyl group or a C3 to C8cycloalkyl group; or R³ and R⁴ may be bonded to each other to form a C3to C7 spiro ring together with the carbon atoms to which they bond; orR¹, R², R³ and R⁴ may form a 5- to 8-membered ring together with thecarbon atoms to which they bond; R⁵ and R⁶ are respectivelyindependently a hydrogen atom or a C1 to C10 alkyl group; Y is a 5- to6-membered aromatic heterocyclic group or condensed aromaticheterocyclic group having one or more hetero atoms selected from anitrogen atom, an oxygen atom and a sulfur atom; the heterocyclic groupmay be substituted with 0 to 6 same or different groups selected fromthe following substituent group α; when the heterocyclic group issubstituted at the two adjacent positions with two alkyl groups, twoalkoxy groups, an alkyl group and an alkoxy group, an alkyl group and analkylthio group, an alkyl group and an alkylsulfonyl group, an alkylgroup and a monoalkylamino group, or an alkyl group and a dialkylaminogroup, all selected from the substituent group α, the two groups mayform, together with the atoms to which they bond, a 5- to 8-memberedring which may be substituted with 1 to 4 halogen atoms; the hetero atomof the heterocyclic group, when it is a nitrogen atom, may be oxidizedto become N-oxide; n is an integer of 0 to 2; wherein said substituentgroup α is selected from the group consisting of hydroxyl group; thiolgroup; halogen atoms; C1 to C10 alkyl groups; C1 to C10 alkyl groupseach mono-substituted with a group selected from the followingsubstituent group β, C1 to C4 haloalkyl groups; C3 to C8 cycloalkylgroups; C1 to C10 alkoxy groups; C1 to C10 alkoxy groups eachmono-substituted with a group selected from the following substituentgroup γ; C1 to C4 haloalkoxy groups; C3 to C8 cycloalkyloxy groups; C3to C8 cycloalkyl C1 to C3 alkyloxy groups; C1 to C10 alkylthio groups;C1 to C10 alkylthio groups each mono-substituted with a group selectedfrom the substituent group γ; C1 to C4 haloalkylthio groups; C2 to C6alkenyl groups; C2 to C6 alkenyloxy groups; C2 to C6 alkynyl groups; C2to C6 alkynyloxy groups; C1 to C10 alkylsulfinyl groups; C1 to C10alkylsulfinyl groups each mono-substituted with a group selected fromthe substituent group γ; C1 to C10 alkylsulfonyl groups; C1 to C10alkylsulfonyl groups each mono-substituted with a group selected fromthe substituent group γ; C1 to C4 haloalkylsulfinyl groups; C1 to C10alkylsulfonyloxy groups each mono-substituted with a group selected fromthe substituent group γ; C1 to C4 haloalkylsulfonyl groups; C1 to C10alkylsulfonyloxy groups; C1 to C4 haloalkylsulfonyloxy groups;optionally substituted phenyl group; optionally substituted phenoxygroup; optionally substituted phenylthio group; optionally substitutedaromatic heterocyclic groups; optionally substituted aromaticheterocyclic oxy groups; optionally substituted aromatic heterocyclicthio groups; optionally substituted phenylsulfinyl groups; optionallysubstituted phenylsulfonyl groups; optionally substituted aromaticheterocyclic sulfonyl groups; optionally substituted phenylsulfonyloxygroups; acyl groups; C1 to C4 haloalkylcarbonyl groups; optionallysubstituted benzylcarbonyl group; optionally substituted benzoyl group;carboxyl group; C1 to C10 alkoxycarbonyl groups; optionally substitutedbenzyloxycarbonyl group; optionally substituted phenoxycarbonyl group;cyano group; carbamoyl group (its nitrogen atom may be substituted withsame or different groups selected from C1 to C10 alkyl groups andoptionally substituted phenyl group); C1 to C6 acyloxy groups; C1 to C4haloalkylcarbonyloxy groups; optionally substituted benzylcarbonyloxygroup; optionally substituted benzoyloxy group; nitro group; and aminogroup (its nitrogen atom may be substituted with same or differentgroups selected from C1 to C10 alkyl groups, optionally substitutedphenyl group, C1 to C6 acyl groups, C1 to C4 haloalkylcarbonyl groups,optionally substituted benzylcarbonyl group, optionally substitutedbenzoyl group, C1 to C10 alkylsulfonyl group, C1 to C4 haloalkylsulfonylgroups, optionally substituted benzylsulfonyl group, and optionallysubstituted phenylsulfonyl group); wherein said substituent group β isselected from the group consisting of hydroxyl group; C3 to C8cycloalkyl groups (which may be substituted with halogen atom or alkylgroup); C1 to C10 alkoxy groups; C1 to C10 alkylthio groups; C1 to C10alkylsulfonyl groups; C1 to C10 alkoxycarbonyl groups; C2 to C6haloalkenyl groups; amino group (its nitrogen atom may be substitutedwith same or different groups selected from C1 to C10 alkyl groups, C1to C6 acyl groups; C1 to C4 haloalkylcarbonyl groups, C1 to C10alkylsulfonyl groups and C1 to C4 haloalkylsulfonyl groups); carbamoylgroup (its nitrogen atom may be substituted with same or different C1 toC10 alkyl groups); C1 to C6 acyl groups; C1 to C4 haloalkylcarbonylgroups; C1 to C10 alkoxyimino groups; cyano group; optionallysubstituted phenyl group; and optionally substituted phenoxy group;wherein said substituent group γ is selected from the group consistingof C1 to C10 alkoxycarbonyl groups; optionally substituted phenyl group;optionally substituted aromatic heterocyclic groups; cyano group; andcarbamoyl group (its nitrogen atom may be substituted with same ordifferent C1 to C10 alkyl groups); and ii) at least one compoundselected from the group consisting of atrazine, simazine, cyanazine,isoxaflutole, mesotrione, flumetsulam, imazethapyr, imazapyr, dicamba,clopyralid, prosulfuron, halosulfuron-methyl, rimsulfuron, bentazone,carfentrazone-ethyl, metribuzin, thifensulfuron-methyl, nicosulfuron,primisulfuron, cloransulam-methyl, glufosinate, glyphosate,glyphosate-trimesium, pendimethalin, linuron, prometryn, diflufenican,flumioxazin, and metolachlor.
 2. The herbicidal composition according toclaim 1, wherein the isoxazoline derivative of the formula (I) or a saltthereof has a substituent selected from the substituent group α on theheterocycle which may be substituted with 0 to 6 same or differentgroups, including hydroxyl group; halogen atoms; C1 to C10 alkyl groups;C1 to C10 alkyl groups each mono-substituted with a group selected fromthe substituent group β, C1 to C4 haloalkyl groups; C3 to C8 cycloalkylgroups; C1 to C10 alkoxy groups; C1 to C10 alkoxy groups eachmono-substituted with a group selected from the substituent group γ; C1to C4 haloalkoxy groups; C3 to C8 cycloalkyloxy groups; C3 to C8cycloalkyl C1 to C3 alkyloxy groups; C1 to C10 alkylthio groups; C1 toC10 alkylthio groups each mono-substituted with a group selected fromthe substituent group γ; C1 to C4 haloalkylthio groups; C2 to C6 alkenylgroups; C2 to C6 alkenyloxy groups; C2 to C6 alkynyl groups; C2 to C6alkynyloxy groups; C1 to C10 alkylsulfonyl groups; C1 to C4haloalkylsulfonyl groups; optionally substituted phenyl group;optionally substituted phenoxy group; optionally substituted phenylthiogroup; optionally substituted aromatic heterocyclic groups; optionallysubstituted aromatic heterocyclic oxy groups; optionally substitutedaromatic heterocyclic thio groups; optionally substituted phenylsulfonylgroups; optionally substituted aromatic heterocyclic sulfonyl groups; C1to C6 acyl groups; C1 to C4 haloalkylcarbonyl groups; optionallysubstituted benzylcarbonyl group; optionally substituted benzoyl group;carboxyl group; C1 to C10 alkoxycarbonyl groups; cyano group; carbamoylgroup (its nitrogen atom may be substituted with same or differentgroups selected from C1 to C10 alkyl groups and optionally substitutedphenyl group); nitro group; and amino group (its nitrogen atom may besubstituted with same or different groups selected from C1 to C10 alkylgroups, optionally substituted phenyl group, C1 to C6 acyl groups, C1 toC4 haloalkylcarbonyl groups, optionally substituted benzylcarbonylgroup, optionally substituted benzoyl group, C1 to C10 alkylsulfonylgroups, C1 to C4 haloalkylsulfonyl groups, optionally substitutedbenzylsulfonyl group, and optionally substituted phenylsulfonyl group);when the heterocyclic group is substituted at the two adjacent positionswith two alkyl groups, two alkoxy groups, an alkyl group and an alkoxygroup, an alkyl group and an alkylthio group, an alkyl group and analkylsulfonyl group, an alkyl group and a monoalkylamino group, or analkyl group and a dialkylamino group, the two groups may form, togetherwith the atoms to which they bond, a 5- to 8-membered ring which may besubstituted with 1 to 4 halogen atoms.
 3. The herbicidal compositionaccording to claim 2, wherein the isoxazoline derivative of the formula(I) or its a salt thereof has a substituent selected from thesubstituent group α0 on the heterocycle which may be substituted with 0to 6 same or different groups, including halogen atoms; C1 to C10 alkylgroups; C1 to C4 haloalkyl groups; C1 to C10 alkoxy C1 to C3 alkylgroups; C3 to C8 cycloalkyl groups (which may be substituted withhalogen atom or alkyl group); C1 to C10 alkoxy groups; C1 to C4haloalkoxy groups; C3 to C8 cycloalkyl C1 to C3 alkyloxy groups;optionally substituted phenoxy group; C1 to C10 alkylthio groups; C1 toC10 alkylsulfonyl groups; acyl groups; C1 to C4 haloalkylcarbonylgroups; C1 to C10 alkoxycarbonyl groups; cyano group and carbamoyl group(its nitrogen atom may be substituted with same or different C1 to C10alkyl groups).
 4. The herbicidal composition according to claim 1,wherein R¹ and R² may be the same or different and are each a methylgroup or an ethyl group; and R³, R⁴, R⁵ and R⁶ are each a hydrogen atom.5. The herbicidal composition according to claim 1, wherein Y is a 5- or6-membered aromatic heterocyclic group having a hetero atom selectedfrom a nitrogen atom, an oxygen atom and a sulfur atom.
 6. Theherbicidal composition according to claim 5, wherein Y is a thienylgroup, a pyrazolyl group, an isoxazolyl group, an isothiazolyl group, apyridyl group or a pyrimidinyl group.
 7. The herbicidal compositionaccording to claim 6, wherein Y is a thiophen-3-yl group, a pyrazol-4-ylgroup, a pyrazol-5-yl group, an isoxazol-4-yl group, an isothiazol-4-ylgroup, a pyridyn-3-yl group or a pyrimidin-5-yl group.
 8. The herbicidalcomposition according to claim 7, wherein Y is a thiophen-3-yl group andthe thiophene ring is substituted with the substituent group α at the 2-and 4-positions.
 9. The herbicidal composition according to claim 7,wherein Y is a pyrazol-4-yl group and the pyrazole ring is substitutedat the 3- and 5-positions with the substituent group α and at the1-position with a hydrogen atom, a C1 to C10 alkyl group, a C1 to C10alkyl group mono-substituted with a group selected from the substituentgroup β, a C1 to C4 haloalkyl group, a C3 to C8 cycloalkyl group, a C2to C6 alkenyl group, a C2 to C6 alkynyl group, a C1 to C10 alkylsulfinylgroup, a C1 to C10 alkylsulfonyl group, a C1 to C10 alkylsulfonyl groupmono-substituted with a group selected from the substituent group γ, aC1 to C4 haloalkylsulfonyl group, an optionally substituted phenylgroup, an optionally substituted aromatic heterocyclic group, anoptionally substituted phenylsulfonyl group, an optionally substitutedaromatic heterocyclic sulfonyl group, an acyl group, a C1 to C4haloalkylcarbonyl group, an optionally substituted benzylcarbonyl group,an optionally substituted benzoyl group, a C1 to C10 alkoxycarbonylgroup, an optionally substituted benzyloxycarbonyl group, an optionallysubstituted phenoxycarbonyl group, a carbamoyl group (its nitrogen atommay be substituted with same or different groups selected from C1 to C10alkyl groups and optionally substituted phenyl group), or an amino group(its nitrogen atom may be substituted with same or different groupsselected from C1 to C10 alkyl groups, an optionally substituted phenylgroup, acyl groups, C1 to C4 haloalkylcarbonyl groups, an optionallysubstituted benzylcarbonyl group, an optionally substituted benzoylgroup, C1 to C10 alkylsulfonyl groups, C1 to C4 haloalkylsulfonylgroups, an optionally substituted benzylsulfonyl group and an optionallysubstituted phenylsulfonyl group).
 10. The herbicidal compositionaccording to claim 7, wherein Y is a pyrazol-5-yl group and the pyrazolering is substituted at the 4-position with the substituent group α andat the 1-position with a hydrogen atom, a C1 to C10 alkyl group, a C1 toC10 alkyl group mono-substituted with a group selected from thesubstituent group β, a C1 to C4 haloalkyl group, a C3 to C8 cycloalkylgroup, a C2 to C6 alkenyl group, a C2 to C6 alkynyl group, a C1 to C10alkylsulfinyl group, a C1 to C10 alkylsulfonyl group, a C1 to C10alkylsulfonyl group mono-substituted with a group selected from thesubstituent group γ, a C1 to C4 haloalkylsulfonyl group, an optionallysubstituted phenyl group, an optionally substituted aromaticheterocyclic group, an optionally substituted phenylsulfonyl group, anoptionally substituted aromatic heterocyclic sulfonyl group, an acylgroup, a C1 to C4 haloalkylcarbonyl group, an optionally substitutedbenzylcarbonyl group, an optionally substituted benzoyl group, a C1 toC10 alkoxycarbonyl group, an optionally substituted benzyloxycarbonylgroup, an optionally substituted phenoxycarbonyl group, a carbamoylgroup (its nitrogen atom may be substituted with same or differentgroups selected from C1 to C10 alkyl groups and an optionallysubstituted phenyl group), or an amino group (its nitrogen atom may besubstituted with same or different groups selected from C1 to C10 alkylgroups, an optionally substituted phenyl group, acyl groups, C1 to C4haloalkylcarbonyl groups, an optionally substituted benzylcarbonylgroup, an optionally substituted benzoyl group, C1 to C10 alkylsulfonylgroups, C1 to C4 haloalkylsulfonyl groups, an optionally substitutedbenzylsulfonyl group and an optionally substituted phenylsulfonylgroup).
 11. The herbicidal composition according to claim 7, wherein Yis an isoxazol-4-yl group and the isoxazole ring is substituted with thesubstituent group α at the 3- and 5-positions.
 12. The herbicidalcomposition according to claim 7, wherein Y is an isothiazol-4-yl groupand the isothiazole ring is substituted with the substituent group α atthe 3- and 5-positions.
 13. The herbicidal composition according toclaim 7, wherein Y is a pyridin-3-yl group and the pyridine ring issubstituted with the substituent group α at the 2- and 4-positions. 14.The herbicidal composition according to claim 7, wherein Y is apyrimidin-5-yl group and the pyrimidine ring is substituted with thesubstituent group α at the 4- and 6-positions.
 15. The herbicidalcomposition according to claim 1, wherein n is an integer of
 2. 16. Theherbicidal composition according to claim 1, wherein the compound ofGroup A is at least one compound selected from the group consisting ofatrazine, cyanazine, simazine and prometryn.
 17. The herbicidalcomposition according to claim 1, wherein the compound of Group A is atleast one compound selected from the group consisting of glyphosate,glufosinate, linuron and flumetsulam.
 18. A herbicidal composition whichcomprises i) the isoxazoline derivative or a salt thereof is a compoundas defined in claim 9 and ii) the compound of Group A is at least onecompound selected from the group consisting of atrazine, cyanazine,simazine, prometryn, glyphosate, glufosinate, linuron, flumetsulam,metribuzin, isoxaflutole, mesotrione, diflufenican, pendimethalin andflumioxazin.
 19. A herbicidal composition which comprises i) theisoxazoline derivative or a salt thereof is a compound as defined inclaim 9 and ii) the compound of Group A is at least one compoundselected from the group consisting of atrazine, cyanazine, simazine andprometryn.
 20. A herbicidal composition which comprises i) theisoxazoline derivative or a salt thereof is a compound as defined inclaim 9 and ii) the compound of Group A is at least one compoundselected from the group consisting of glyphosate, glufosinate, linuronand flumetsulam.
 21. The herbicidal composition according to claim 1,wherein ii) at least one compound of Group A is comprised in an amountof from 0.001 to 100 parts by weight to 1 part by weight of i) anisoxazoline derivative represented by the Formula (I) or a salt thereof.22. The herbicidal composition according to claim 1, which is used as anagrochemical product comprising i) an isoxazoline derivative of theFormula (I) or a salt thereof and ii) at least one compound of Group Ain a total amount of from 0.5 to 90 wt %.